Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3q26.3,
ENSEMBL_GENE_ID ENSG00000121879,
GENERIF_SUMMARY In squamous cell carcinomas the negative effect of p53 induction on cell survival involves transcriptional inhibition of PIK3CA that is independent of PTEN activity, as PTEN is not expressed in the primary tumors, agonist binding to Gq-coupled receptors blocks Akt activation via the release of active Galphaq subunits that inhibit PI3K via an inhibitory interaction between Galphaq and p110alpha PI3K., data suggest that mutant PIK3CA is likely to function as an oncogene in human cancers; PIK3CA may prove useful for diagnostic and therapeutic purposes, Missense Mutation in PIK3CA is associated with breast cancers, Mutations of PIK3CA is associated with anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas, oncogenic mutations in human cancers, Genetic alterations of class IA PI3K subunit genes can occasionally play a role in human glioblastoma by activating the PI3K-AKT signaling pathway independently of PTEN mutation., Data show that glucose is a crucial regulator of V-ATPase in renal epithelial cells and that the effect of glucose is mediated by phosphatidylinositol 3-kinase (PI3K)., determined the growth-regulatory and signaling properties of the three most frequently observed PIK3CA mutations, PIK3CA mutations in exons 9 & 20 were directly sequenced. A novel silent mutation was found. PIK3CA mutation may be an early event in ovarian carcinogenesis., Activation of the PI3K signalling pathway in gastric cancer may be achieved through up-regulation or mutation of PIK3CA, in which the latter may be a consequence of mismatch repair deficiency., Mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications for breast cancer., Data indicate that mutations of PIK3CA play an oncogenic role in substantial fractions of ovarian and breast carcinomas., mutation of the PIK3CA gene is not common, but its amplification is relatively common and may be a novel mechanism in activating the PI3K/Akt pathway in some thyroid tumors, Colon cancer-associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis., Amino acid substitutions in PIK3CA from human colorectal cancer cell lines constitutively activate the AKT pathway, and consequently, promote tumor cell growth and invasion., PI-3 kinase p110alpha subunit expression and recombinant heparin-binding epidermal growth factor-like growth factor (HB-EGF) synergistically decrease inducible nitric oxide synthase expression and nitric oxide production in intestinal epithelial cells, copy number gains, instead of mutation, may be a common mechanism for activation of PIK3CA in tumorigenesis of primary nasopharyngeal carcinoma, an important role of PIK3CA gene aberrations in the molecular pathogenesis of primary glioblastomas, this study has shown that the mutations detected in the helical and kinase domains of PIK3CA do not seem to affect the PI3-K pathway characteristics of the eight cell lines studied, The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer., analysis of PIK3CA mutations in ovarian cancer [letter], increased activation state of AKT kinase appears to be present in cervical carcinogenesis, and may be accounted for by PIK3CA amplification, whereas PTEN mutation seems to be of little importance, Mutant PIK3CA is likely to function as an oncogene in anaplastic thyroid cancer and less frequently well-differentiated thyroid carcinomas., PIK3CA mutations are associated with breast cancer, Data show that alpha6 and alpha3 integrin subunits interact with laminin 5 to increase expression of E-cadherin, and suggest that phosphoinositide 3-kinase (PI 3-kinase) activation plays a key role in this cross-talk., although introduction of activating mutations from p110alpha at the corresponding sites in p110beta failed to render the enzyme oncogenic in human cells, the possibility remains that other mutations might activate the beta isoform, cancer-specific mutations in PIK3CA have made p110alpha an ideal drug target [Review], A mutation status profile of the PIK3Ca gene in the National Cancer Institute (NCI)-60 panel of human cancer cell lines provides insights into the role of mutant PIK3Ca in oncogenic signaling, study extends previous observations in other tumor types by demonstrating presence of somatic PIK3CA mutations in both SCC and adenocarcinoma of the esophagus, thus implicating the PI3K pathway in the initiation and/or progression of esophageal cancers, These results indicate that PI3K plays different roles in the activation of Ras/ERK1/2 signaling by insulin and EGF, and that insulin-stimulated, but not EGF-stimulated, ERK1/2 and Akt signalings diverge at PI3K., AT(1) receptor-mediated activation of PI 3-K/Akt cascades occurs at least partially via the transactivation of EGF receptor, which is under a negative control by AT(2) receptor in hypertrophic scar fibroblasts., PIK3CA mutations are associated with head and neck squamous cell carcinoma, Although a key factor in TRAF6-dependent activation of PI 3-kinase, ectopic expression of Src was insufficient for NF-kappaB activation and, in contrast to NF-kappaB, was not inhibited by IRAK2., Mutation of PIK3CA is associated with breast cancer, Somatic mutations of PIK3CA, encoding p110alpha catalytic subunit of Class IA PI3Ks, have been found in various cancers., inhibition of PI 3-kinase activity reduced hypoxic HIF-1alpha protein levels to a similar extent as serum deprivation, PI3K-IA activity is necessary for both high NaCl- and ionizing radiation-induced activation of ATM and (ii) high NaCl activates PI3K-IA, which, in turn, contributes to full activation of TonEBP/OREBP via ATM., Various mutations in a variety of cancers, including a pseudogene and polymorphisms., p110alpha play an important role in tumor growth by inducing angiogenesis and by increasing HIF-1alpha and VEGF expression. This work provides a better understanding of the molecular mechanism of human cancer induced by the activation of PI3K signaling., First report of PIK3CA mutation in pancreatic cancer, providing evidence of its oncogenic properties., Increased expression for PIK3CA mrna is associated with regional lymph node metastasis in esophageal squamous cell carcinoma, Acidic pH exposure protects HEMEC through induction of Hsps and activation of MAPK and PI3 kinase pathway., PIK3CA amplification is uncommon and appears to be late event in the development of ethmoid sinus adenocarcinoma., TGF-beta1 regulates COX-2 expression in human mesangial cells through the activation of ERK1/2, p38 MAPK, and PI3K., Pik3ca, Ras family, and Braf activating mutations occur rarely in human neuroblastomas or in a murine model driven by neural-restricted MYCN overexpression., These studies demonstrate that induction of fibulin 5 gene expression in lung fibroblasts is mediated via canonical TGF-beta/Smad signaling and requires the PI3-kinase/Akt pathway., The expression of p110alpha siRNA significantly decreased cell migration, invasion and proliferation., Outside-in signaling via P2Y12 and both PI3Kbeta and PI3Kgamma isoforms is required for maintenance of a platelet aggregate., PIK3CA mutations were strongly associated with FGFR3 mutations in superficial papillary bladder tumors., PIK3CA mutation incidence was significantly lower in lung adenocarcinoma than in lung squamous cell carcinoma; among eight patients with a PIK3CA mutation, three patients also harbored an EGFR somatic mutation., results confirm that PIK3CA mutations are frequent in endometrial carcinoma and support the hypothesis that PIK3CA mutations may have an additive effect to PTEN monoallelic inactivation in endometrial carcinoma, PI3K is an important intracellular regulator of epidermal homeostasis and repair., It has recently been shown that Akt activation is associated with a worse outcome among endocrine treated breast cancer patients and that it also inhibits the progesterone receptor (PR) expression via the PI3K/Akt pathway in breast cancer cells., This is the first study showing PIK3CA mutations in pediatric glioblastomas, thus providing a molecular target in this important pediatric malignancy., Mutations of the PIK3CA gene is associated with the development of oral squamous cell carcinoma, Activation of PI3K signaling by mutations in PTEN or PIK3CA can lead to activation of p53-mediated growth suppression., PIK3CA may serve as a marker of invasion in endometrial cancer., Results show that coculture with ECs enhances VSMC adhesion and spreading by up-regulating beta(1)-integrin expression and activating the PI3K/Akt pathway. Interaction between ECs and VSMCs serves a role in vascular homeostasis and remodeling., PIK3CA mutations might exert their effects through activation of the phosphatidylinositol 3-kinase/AKT/ER-alpha pathway, Results indicate that stimulation of heme oxygenase-1 expression by hypericin-PDT is a cytoprotective mechanism governed by the p38(MAPK) and PI3K pathways., PIK3CA exon 9 and exon 20 rarely mutate in nasopharyngeal carcinoma., PIK3CA alterations in primary (de novo) and secondary glioblastomas., Thus EPO promotes survival of endothelial cells through PI3K-dependent Bcl-x(L)-induction and BIM regulation, as well as through a separate mechanism involving the ERK pathway., These results demonstrate that hypoxic condition-and high cell density-induced expression of Redd1 is mediated by coactivation of Sp1 and HIF-1alpha downstream of the PI3K/Akt signaling pathway., These results suggest that there is a fine distinction between the signaling activators and downstream effectors of the oncogenic PI3K and RAS pathways in breast epithelium and those in other tissues., The data suggest that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate., These data demonstrate that IGF-I induces COX-2 expression in human ovarian cancer cells, which is mediated by three parallel signaling cascades--PI3K, MAPK, and PKC pathways that differentially regulate COX-2 expression., studies show that mutant PIK3CA increases the capacity for proliferation and survival under environmental stresses, such as growth factor deprivation stress while also imparting greater dependency on the PI3K pathway for proliferation and survival, p110alpha PI-3K appears to uniquely regulate important monocyte functions, where other PI-3K isoforms are uninvolved or unable to fully compensate., PIK3CA mutations may have a role in cancer, PIK3CA amplification and Ki-67 index were strong predictors for an early tumor-associated death in ovarian cancer patients., data from a Chinese cohort provide further genetic evidence suggesting that dysregulated PI3K/Akt pathway plays a significant role in the pathogenesis of thyroid tumors, TLR3, PI3K, and IRF3 are involved in the poly IC-induced galectin-9 expression in HUVECs, PI3K/ILK/Akt/NF-kappaB axis is a promising target for therapeutic intervention in renal cell carcinoma., Data suggest that lipid rafts play critical roles in KSHV infection and gene expression, probably due to their roles in modulating KSHV-induced PI3-K, RhoA-GTPase, and Dia-2 molecules essential for postbinding and entry stages of infection., Data suggest that PIK3CA mutations contribute to the invasion step from intramucosal carcinoma to invasive carcinoma in colorectal carcinogenesis., PIK3CA copy number gain and amplification is associated with head and neck squamous cell carcinoma, PIK3CA mutations and PTEN loss were not mutually exclusive events and associated with similar prognostic factors, Whereas PI3K is downstream of MUC1 activation and negatively regulates TLR5 signaling, it is not responsible for MUC1-induced suppression of TLR5 signaling., PIK3CA mutation was significantly associated with shorter relapse-free survival in stage II/III patients, and shorter disease-specific survival in all patients., Phosphoinositide 3-kinase-independent non-genomic signals transit from the androgen receptor to Akt1 in membrane raft microdomains, PIK3CA mutations are mutually exclusive with PTEN loss in diffuse large B-cell lymphoma, Coexistent mutations/epigenetic inactivations in PI3K/AKT pathway may be responsible for the unusually aggressive course of ACC., oncogenic PIK3CA mutations contribute to the pathogenesis of skin tumors lacking malignant potential, There was significant difference in survival between the lung cancer patients with PIK3CA normal copy number and the patients with PIK3CA amplification, PIK3CA has an important role in human lung carcinogenesis, possibly by promoting malignant transformation., IGF-1 plays a role in potentiating platelet aggregation by complementing G(i)- but not G(q)-signaling pathways via PI3-K p110alpha., plexin-B1 promotes endothelial cell motility through RhoA and ROK by regulating the integrin-dependent signaling networks that result in the activation of PI3K and Akt, Data suggest that PI3K-C2beta and AKT are epistatic to intersectin, and show that ITSN, independent of its role in endocytosis, regulates a critical cellular signaling pathway necessary for cell survival., The three most common tumour-derived alleles of p110alpha were shown to potently activate phosphoinositide 3-kinase signalling in human epithelial cells., Engagement of NKG2D by itself is sufficient to stimulate the formation of the natural killer cells immunological synapse (NKIS), with recruitment of NKG2D to the center synapse., High levels of p-AKT expression occurred independently of the presence of PTEN or PIK3CA mutations in endometrial cancer., In trastuzumab-treated breast cancer patients combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone., rotavirus-induced PI3K activation causes regulation of integrin expression in intestinal cells, leading to prolonged adherence of infected cells to collagen and increased virus production., exon 9 PIK3CA mutations are typical of infiltrating lobular carcinomas, The C allele of rs361072 attenuates insulin resistance in superobese European children., The results presented here indicate that actin reorganization through FAK/PI3-K/Rac-1 activation operates in various human cancer cell systems supporting a functional role for FAK/PI-3K/Rac1/actin signaling in controlling cell motility., An impaired control of glycogen synthase kinase-3beta activity by insulin receptor-mediated signalling plays a role in the pathogenesis of AD, facilitating tau protein phosphorylation and neurofibrillary tangle formation., Using both direct genomic DNA sequencing and novel mutant-enriched sequencing methods developed specifically for the 3 hot-spot mutations (H1047R, E545K and E452K) of PIK3CA, we detected 5 mutations of PIK3CA in the 24 pharyngeal cancers (20.8%)., A higher incidence of PIK3CA alterations and the possible synergistic effect of these alterations and BRAF mutations suggest their major role in Middle Eastern papillary thyroid neoplasms., Sexual dimorphisms and tissue specific factors might directly or indirectly influence the occurrence of PI3KCA cancer alleles., These data provide the first evidence that IL-18 and FN stimulate each other's expression, Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for alpha-platelet-derived growth factor receptor-induced production of reactive oxygen species., different PIK3CA mutations differentially contribute to breast cancer transformation, study reports a 3.0 angstrom resolution structure of a complex between p110alpha and a polypeptide containing the p110alpha-binding domains of p85alpha; results suggest specific mechanisms for the effect of oncogenic mutations in p110alpha and p85alpha, PIK3CA mutations are associated with myometrial invasion and tumors with PIK3CA mutations in exon 20 are frequently high-grade, invasive endometrial carcinomas., PIK3CA mutations in HNSCC are likely to be oncogenic and may significantly contribute to HNSCC carcinogenesis and pave attractive target for therapeutic prevention., In this study, we were unable to find a clear association between PIK3CA mutations and gene amplifications, nor with tumor histological subtypes or staging, somatic PIK3CA mutations contribute to the frequent activation of the PI3K/AKT pathway in carcinomas of the biliary tract and liver, PIK3CA mutations are common in invasive ductal carcinomas of the breast and PIK3CA exon 20 mutation is an independent risk factor for poor prognosis in breast cancer patients., analysis of PIK3CA mutations in Saudi Arabian colorectal cancer patience, Poliovirus simultaneously activates the phosphatidylinositol 3-kinase (PI3K)/Akt survival signaling pathway in these cells, limiting the extent of JNK activation and thereby cell death., genetic alterations of KRAS and PIK3CA may play equivalent roles in endometrial carcinogenesis, Mutations in the PIK3CA is associated with colon cancers, In exon 9, a somatic mutation was found in two patients (2.2%) and in two cell lines; mutations included three E545K (G1633A) mutations and one E545Q (G1633C) mutation, in exon 20, no mutation was observed in our esophageal cancer patients, The demonstration that p53 binds directly to the PIK3CA promoter and inhibits its activity identifies a novel mechanism whereby these two mediators regulate cellular functions., PI3Kalpha and -beta present distinct activation requirements and kinetics in G(1) phase, with a selective action of PI3Kalpha at the G(0)/G(1) phase transition, point mutations in the p110alpha subunit of class IA PI3K confer factor independence to hematopoietic cells in vitro and leukemogenic potential in vivo, but have lower transforming activity than a deregulated class III receptor tyrosine kinase., identified and characterized the PIK3CA 5' upstream transcriptional regulatory region and confirmed that PIK3CA is transcriptionally regulated through NF-kappaB pathway, Our data provide evidence that PIK3CA and BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS., high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma., PIK3CA mutation was associated with a decreased rate of node-positive disease, particularly among ER-positive tumors., PIK3CA is rarely mutated in diffuse large B-cell lymphoma, structure of the complex between the catalytic subunit of PI3Kalpha, p110alpha, & a portion of its regulatory subunit, p85alpha reveals the majority of the oncogenic mutations occur at the interfaces between p110 domains & between p110 & p85 domains, results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis, FGFR3 and PIK3CA germline mutations can be excluded as an underlying genetic basis, therefore alternative mechanisms have to contribute to familial Seborrheic Keratoses., PIK3CA mutation is significantly associated with key molecular events in colorectal cancer, and MGMT loss likely contributes to the development of PIK3CA G>A mutation, Overexpression of PI3K and Akt is associated with malignant rhabdoid tumor, KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab., PIK3CA mutations, in comparison with PTEN loss and AKT1 mutations, were associated with significantly less and inconsistent activation of AKT and of downstream PI3K/AKT signaling in tumors and cell lines, Exon 20 PIK3CA mutations are relatively frequent in Her-2+ breast tumors and shorten survival, whereas neither exons 9 and 20 mutations seem related with "triple negative" breast carcinomas, study identified a potential hotspot for resistance mutations (I800), a drug-sensitizing mutation (L814C), and a surprising lack of resistance mutations at the "gatekeeper" residue, RNA interference-mediated knockdown of PIK3CA inhibited colony formation of cell lines with PIK3CA mutations or gains but was not effective in PIK3CA wild-type cells. PIK3CA mutations or gains are present in a subset of lung cancers, TGFbeta activates PI3K to downregulate PTEN for enhancement of cell proliferation that is independent of SMAD proteins, BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis, Inhibitors that target exclusively the cancer-specific mutants of p110 alpha constitute an important goal and challenge for current drug development., Higher BRCA1 mRNA expression is significantly correlated with advanced disease and ERBB2 overexpression in breast cancers., In tumors with co-occurring mutations in multiple components of the PI3K pathway, selective inhibition of the alpha isoform of p110 is an attractive therapeutic strategy, especially for late-stage tumors., These data establish a new function for the NBS1 protein as a regulator of PI3K activity via SFK members., strong genetic evidence supporting a role of the PI3K/AKT signaling pathway in the tumorigenesis of pituitary tumors, particularly the invasive types, Mutant-specific differences in the catalytic cleft and activation loop behavior suggest that structure-based mutant-specific inhibitors can be designed for PIK3CA-positive breast cancers., our data reveal a novel function of p110alpha in medulloblastoma growth and survival., ARF1 regulates epidermal growth factor-dependent breast cancer cell growth and invasion during cancer progression by controlling the activation of the phosphatidylinositol 3-kinase pathway, JAK2, EGFR and PI3KCA hot spot mutations are uncommon in endocrine tumors, The result showed that the mutation rate of PIK3CA in nasopharyngeal carcinomas (n = 73) was 9.6%, whereas both BRAF (n = 65) and RAS (n = 45) were wild type in every specimen with adequate DNA for analysis., data showed a higher incidence of PIK3CA mutations in Malaysian breast cancers compared to colorectal & nasopharyngeal tumor tissue; findings also indicate PIK3CA mutations play a pivotal role in activation of the PI3 K signaling pathway in breast cancer, PIK3CA amplification and single nucleotide polymorphism may be a marker predicting ovarian cancer response and resistance to chemotherapy., inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers, Zinc sulfate stimulation could activate the EGFR and the PI3K/Akt signaling pathway, further leading to upregulation of ICAM-1 expression in human airway epithelial cells., results suggest that FGFR3 and PIK3CA mutations are involved in the pathogenesis of solar lentigo and occurrence of these mutations in both SL and SK suggests a common genetic basis., a selective downregulation of the p110alpha catalytic isoform in pregnancy, Missense mutations of PIK3CA are identified in 81% of cervical cancer cell lines, with mutation rate higher in older women., genetic variations in PIK3CA may be associated with survival in esophageal cancer, activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras, findings suggest GSK3beta is an important effector of mutant PIK3CA, and that lithium, an FDA-approved therapy for bipolar disorders, has selective antineoplastic properties against cancers that harbor these mutation, PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies., In this study they investigated the effect that the two major classes of PIK3CA mutation have on the biochemical properties of p110alpha., PIK3CA mutations are frequent events in endometrial carcinomas of any histological type, Compared with patients with PIK3CA wild-type tumors, those with PIK3CA-mutated tumors experienced an increase in colon cancer-specific mortality according to univariate analysis., Amplifications of 3q26.32 harboring the oncogene PIK3CA were associated with poor prognosis and segregated with the aggressive transcriptional cluster., In the current study of primary uterine serous carcinoma (USC) tumors, oncogenic mutations of the PIK3CA gene were seen in 15% of USC cases, There was an association of PIK3CA mutation (kinase domain) with increased androgen receptor levels in breast cancer., low frequency of PIK3CA mutations in CLL suggests that such mutations are unlikely to cause any major transforming activity in CLL in general., Frequent activating mutations of PIK3CA is associated with ovarian clear cell carcinoma., PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer., GILZ1 and SGK1 provide a physical and functional link between the PI3K- and Raf-1-dependent signaling modules, PIK3 kinase expression is higher in metastatic melanoma., This study for the first time uncovered PIK3CA alterations in small cell lung cancer, complete concordance of PIK3CA and AKT1 mutations in matched samples of invasive and in situ tumor indicates that these mutations occur early in breast cancer development, Mutation E17K/AKT1 was not detected in the 24 samples of retinoblastoma analyzed. K-RAS mutations were identified in two samples. There were no mutations in any of the other genes analyzed., RNA interference-mediated silencing of the phosphatidylinositol 3-kinase catalytic subunit attenuates growth of ovarian cancer., oncogenic properties of KRAS and BRAF but not NRAS, HRAS, and PIK3CA contribute to the tumorigenesis of periampullary and ampullary tumors, results suggest that genetic alterations in the PI3K pathway are common in prostate cancer, and occur mainly through PIK3CA amplification and PTEN hemizygous or homozygous deletion, Absence of PIK3CA/AKT1 mutations in one specimen may not reflect the status at other sites because these mutations arise during progression., PI3-K accelerates the short course of GPIb centralisation for two PAR signal pathways during the course of thrombin receptor activation in platelets., Phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer; PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis in breast cancers, Findings show that PI3K inhibition diminished hepatoblastoma cell growth being accompanied by reduced AKT and GSK-3beta phosphorylation., PIK3CA (P=0.01) mutations predicted reduced progress free survival in response to cetuximab salvage therapy in patients with metastatic colorectal cancer ., Data show that no mutations were detected in PIK3CA and CTNNB1/beta-catenin hotspot sequences., SHIP gene can inhibit K562 cell proliferation and promote cell apoptosis via inactivating PI3K/Akt pathway., PIK3CA mutations are associated with resistance to HER2-targeted agents., Investigated PI3K/AKT genetic alterations such as PIK3CA amplification, PIK3CA mutation, PTEN protein loss. PIK3CA amplification was seen in 54 of 152 epithelial ovarian cancer (EOC) cases analyzed., Nicotine increases PPARbeta/delta gene expression through alpha7 nAChR-mediated activation of PI3K/mTOR signals that inhibit AP-2alpha protein expression and DNA binding activity to the PPARbeta/delta gene promoter., Positive prognostic significance of PIK3CA mutations in breast cancer., a link between PI3K(p110alpha) and atrial fibrillation, Associations between PIK3CA expression and clinicopathological variables, molecular classes, and patients' outcome were investigated. PIK3CA is an oncogenic biomarker associated with poor prognosis in breast cancer., Mutation analysis showed activation mutations in the PIK3CA gene in tumors that also had DNA copy number increases in the PIK3CA locus, suggesting an additive effect of coexisting activating amino acid substitution and dosage increase from amplification., association of PIK3CA gene amplification with worse prognosis in nasopharyngeal carcinoma., PI3K pathway alterations are common in bladder cancer., VDR overexpression in colorectal cancer is independently associated with PIK3CA and KRAS mutations., The structural and biochemical data suggest a previously undescribed mechanism for mutational activation of PIK3CA that involves perturbation of its interaction with the cellular membrane., phosphoinositide 3-kinase isoforms alpha and beta have roles in glycoprotein VI-induced platelet signaling and thrombus formation, PIK3CA mutations mostly began to develop at the stage from the DIN1B to the carcinoma in situ (DCIS), which is a late event of breast oncogenesis., Age-associated changes in transgenic murine heart lead to suppression of the p110 alpha isoform of phosphoinositide 3-kinase activity that modifies cardiac aging., Rare mutations in the PIK3CA gene contributing to aggressive endometrial cancer - has been shown., PIK3CA KD mutation was a favorable prognostic factor for relapse-free survival in response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer., Three of five stucco keratosis samples revealed a PIK3CA mutation(E542K, E545K), but no FGFR3 mutation was found. In contrast, both dermatosis papulosa nigra samples harboured an FGFR3 mutation (R248C, S249C) but no PIK3CA mutation., In hereditary breast cancer, PIK3CA mutations were found only in the BRCA2 group., PI3K physically interacts with the glucocorticoid receptor (GR)through two putative PI3K recruitment consensus YxxM binding motifs in the GR suggesting that some functions regulated by this receptor might occur through kinase interaction., Aurora-A, via activating Akt, stimulated nuclear factor-kappaB signaling pathway to promote cancer cell survival., approximately two-thirds of papillomas are driven by mutations in the PI3CA/AKT pathway, PIK3CA mutations may have a role in recurrence of rectal cancer, Tumors expressing the p110alpha helical domain mutant showed a increase in tumor cell intravasation into the blood and tumor cell extravasation into the lung compared with tumors expressing wild-type p110alpha or the kinase domain mutant., Leptin plays an important role in papillary thyroid carcinoma pathogenesis through PI3K/AKT pathway via Ob-R and is a potential prognostic marker associated with an aggressive phenotype and poor disease-free survival., PI3K/AKT mutations may not play a major role in multiple myeloma., These findings demonstrate the importance of cross-talk between the PI3K/Akt and beta-catenin pathways in medulloblastoma, PI3-kinase regulates the thrombin-induced actin cytoskeleton reconstitution in platelets by the RhoA-mDia1 pathway., Expression of PIK3CA was higher in the hepatocellular carcinoma tissue than in the corresponding adjacent tissue., mutations in critical genes within the PI3-kinase (PI3K) pathway are not functionally equivalent, and that other cooperative genetic events may be necessary to achieve oncogenic PI3K pathway activation in cancers that contain the AKT1 E17K mutation., Data show that similar responses were seen in cancer cells with wild-type or activated mutant PI3K genes treated with p110alpha/delta or p110alpha/beta/delta inhibitors in cell viability assays., PIK3CA mutations were detected in 13/46 (28%) plasma-derived and 10/46 (21%) serum-derived cfDNA samples from metastatic breast cancer patients., The results showed that inhibition of PI3K and Akt-2 was associated with reduced SREBP-1 activation by genotype 3a hepatitis c virus core protein., TLR2 cooperates with MyD88, PI3K, and Rac1 in lipoteichoic acid-induced cPLA2/COX-2-dependent airway inflammatory responses, PIK3CA alterations specifically correlate with clinicopathological characteristics of Bulgarian patients with breast cancer., We evaluated the presence of mutations in PIK3CA, AKT1, AKT2, AKT3, PTEN, and PDPK1 genes in 83 papillary thyroid carcinomas, Data show that PTPN11 mutations causing Leopard syndrome (LS) facilitate EGF-induced PI3K/AKT/GSK-3beta stimulation through impaired GAB1 dephosphorylation, resulting in deregulation of a novel signaling pathway that could be involved in LS pathology., The p110alpha selectively mediates activation of the Tyr kinase Pyk2 to regulate barrier function., Mutant PIK3CA interferes with apoptosis downstream of death receptor-signal complex, allowing caspase-8 activation without apoptosis. Cleavage of ROCK-1 by caspase-8 triggers amoeboid shape and invasiveness of HCT116 cells in response to TRAIL and CD95L., PIK3CA mutations in gastric carcinoma may be a signature of cancer type, No hotspot mutations were detected in any of the samples. PIK3CA hotspot mutations are unlikely to play a major role in the pathogenesis of OSCC in the Greek population., Although the PIK3CA gene signature was not associated with prognosis in ER- and HER2+ breast cancer, it could identify better clinical outcomes in ER+/HER2- disease., Studies indicate that the high-frequency somatic mutations of PIK3CA observed in different human cancers further strengthen the notion that PI3Ks are optimal targets for therapeutic intervention., Direct sequencing analysis of endometrial DNA analysis did not reveal any activating somatic mutations in either PI3KCA or AKT1 gene, indicating that these mutations are rarely associated with endometriosis in South Indian women., Decreased expression of PTEN together with overexpression of PI3K and AKT contribute to gastric cancer progression., the relevance of PIK3CA mutations to a wide range of common human tumor types (Review), Results suggest that mutation of PIK3CA is an early event in breast cancer that is more likely to play a role in breast tumor initiation than in invasive progression. A role for exon 9 mutations in the progression of a subset of DCIS cannot be excluded., Activation of the PI3K/AKT signalling pathway in non-melanoma skin cancer is not mediated by oncogenic PIK3CA and AKT1 hotspot mutations., reports the low frequency of PIK3CA and B-RAF mutations in astrocytomas, despite the presence of activated ERK and AKT proteins., PIK3CA mutations may have a role in KRAS and BRAF wild type colorectal cancer, Oncogenic mutations of PI3Kalpha result in a constitutively activated enzyme that triggers downstream pathways that increase tumor aggressiveness and survival (Review), PIK3CA HRMA assay was evaluated by performing repeatability, sensitivity, and comparison with DNA sequencing studies and was further validated in 129 formalin-fixed paraffin-embedded breast tissue samples, if KRAS is not mutated, assessing BRAF, NRAS, and PIK3CA exon 20 mutations (in that order) gives additional information about the efficacy of cetuximab plus chemotherapy in metastatic colorectal cancer., PIK3CA rs7651265 GG genotype was associated strongly with colon and rectal cancer., mediates activation of TGF-beta2 promoter response elements leading to high cytokine expression in cancer cells, Hyaluronic acid and thrombin increase protein synthesis of MT1-MMP and activate mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and Rac-1 signaling pathways in homing of hematopoietic stem/progenitor cells., Genetic ablation of the mutant PIK3CA allele in MEK inhibitor-resistant cells restores MEK pathway sensitivity, re-expression of mutant PIK3CA reinstates resistance, highlighting the importance of this mutation in resistance to therapy in cancers., Data show that DLBS1425 significantly reduced phosphoinositide-3 (PI3)-kinase/protein kinase B (AKT) signalling by reducing PI3K transcript level and subsequent reduction in AKT phosphorylation., Data show that the mutations weaken an inhibitory interaction between p85alpha and p110alpha., Sodium butyrate increased PTEN expression, promoted the expression of MUC2 and induced the differentiation of gastric cancer cells through the PTEN/PI3K signalling pathway., study supports that mutations in the PIK3CA gene make at least a minor contribution to OSCC tumorigenesis, PIK3CA mutation is associated with poor trastuzumab response in HER2-positive metastatic breast cancer., The levels of total Akt and phosphorylated Akt (active Akt) are increased in E6-AP overexpressing prostate gland and LNCaP cells suggesting that E6-AP regulates the PI3K-Akt signaling pathway., STC1 induction by thyroid hormone depends on both TRbeta and PI3K activation., Findings suggest that there is p70S6K-mediated, cross-inhibitory regulation between the MEK/ERK and PI3K/mTOR pathways, in which each contribute to the maintenance of the self-renewal and tumorigenic capacity of glioblastoma glioblastoma stem-like cells, Mutations in PIK3CA is associated with squamous cell carcinomas of the lung., PIK3CA mutants overall showed a significantly longer time to first recurrence than wild type cases, the p110alpha and beta isoforms of class IA PI3K are both required for the proinflammatory response to flagellin via TLR5, Up-regulation of PIK3CA may promote the metastasis of gastric cancer through aberrant activation of PI3K/Akt., cIAP2 upregulated by E6 via EGFR/PI3K/AKT cascades may contribute to cisplatin resistance, revealing that the EGFR or PI3K inhibitor combined with cisplatin may improve the chemotherapeutic efficacy in HPV-infected lung cancer., the PI3K/AKT signaling pathway is aberrantly active and plays a critical role for the cell cycle progression in human pleural mesothelioma cells., findings indicate that somatic mutations in KRAS and PIK3CA but not BRAF oncogenes are closely associated with the development of cholangiocarcinoma in Chinese population, Combined inhibition of PI3K and mTOR, which activates autophagy without activating Akt, cooperated with inhibition of autophagy to cause glioma cells to undergo apoptosis., Although the mechanism of load-induced mTORC1 activation remains to be determined, it is clear that it does not require classical growth factor signaling., Data show that of primary tumors 64% were mutant for FGFR3, 11% for RAS, 24% for PIK3CA, and 26% for p53., Expressions of Akt1, Akt2 and PI3K were decreased in ovarian epithelial cancer cells transduced with PTEN., Common genetic variation in PTEN, PIK3CA, AKT1, MLH1, or MSH2 was not statistically significantly associated with endometrial cancer., Data show that among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%)., PI3K signaling pathway is activated by PIK3CA mRNA overexpression and copy gain in prostate tumors., Activation of the PI3K/AKT in addition to MAPK/ERK signaling pathways may underlie biological aggressiveness in pilocytic astrocytoma (PA). Specifically, it may mediate the increased proliferative activity observed in histologically anaplastic PA., In hyperglycemic leptin-deficient Lep(ob/ob) transgenic mice, leptin acutely and potently improves glucose metabolism, before any change of body fat mass, via a mechanism involving the p110alpha and -beta isoforms of phosphatidylinositol-3-kinase (PI3K)., down-regulation of PI3K-C2alpha may be a feature of type 2 diabetes., Mutations in PIK3CA, KRAS and NRAS were exclusive to tumors of uterine origin and age-adjusted Cox proportional hazards modeling associated advanced age, stage and TP53 mutations with decreased survival in the uterine subset., PIL3Ca mutations may not only be a prognostic factor, but may also be predictive of preoperative radiation benefit., Data support the idea that PI3Kalpha plays an important role in the metastatic process and suggest a more informed strategy for selecting drugs worthy of further development for clinical application., Results suggest that low magnitude stretch can induce cPLA(2) phosphorylation through the MEK/ERK and PI3K-Akt pathways, independently., Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-delta in normal human dermal fibroblasts., the PI3K/PAK1/ERK signaling pathway has a role in LPA-stimulated breast cancer cell migration, PIK3CA mutation and the Wnt pathway have roles in ERalpha-positive breast cancer, EGFR, PI3Kp110 and PTEN expression is a common feature of neuroblastoma, Here, the authors show that VP11/12 is required for virus-induced activation of PI3K-Akt signaling in herpes simplex virus 1-infected Jurkat T cells and primary fibroblasts., study identified one PIK3CA missense mutation in pancreatic neuroendocrine tumors, Data show that the effects of PI3K-Akt signalling on IL-10 responses were mediated at least in part by GSK3., PIK3CA mutations are associated with drug resistance in non-small cell lung cancer., analysis of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas, PI3K/AKT/mTOR signalling pathway activation is a common event in high-risk neuroblastoma., Data suggest that the PI3K/Akt pathway is involved in apoptotic function in PKHD1-silenced cells, and PI3K/Akt inhibition correlates with upregulation of NF-kappaB activity., The presence of activating mutations in PIK3CA specifically in gallbladder cancer has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors., The importance of PIK3K/PAK in neoplasm transformation and progression, their disregulation detected in oral squamous cell carcer may provide early diagnosis and aid in the design of new therapies., PIK3CA mutations were rare in colorectal laterally-spreading tumors., Report novel hotspot PIK3CA mutation in Iranian breast cancer patients., PI3K-activating hormones inhibit ROMK by enhancing its endocytosis via a mechanism that involves phosphorylation of WNK1 by Akt1 and SGK1., Phosphatidylinositol 3'-kinase signaling pathway is essential for Rac1-induced hypoxia-inducible factor-1(alpha) and vascular endothelial growth factor expression in hypoxia., demonstrate here that breast cancer cells harbouring PIK3CA mutations are selectively sensitive to mTOR allosteric and kinase inhibitors. However, cells with PTEN loss of function are not sensitive to these drugs, Thus, sendai virus infection-mediated apoptosis is temporally regulated by the prevention of XIAP degradation by PI3K., Studies suggest that dual PI3K and mTOR inhibition using NVP-BEZ235 may be an effective novel therapeutic approach in patients with ovarian cancer., Our data demonstrate that PIK3CA is a mediator of collagen I-induced down-regulation of E-cadherin., Results show the mechanism by which EZH2 regulates BRCA1 expression and genomic stability mediated by the PI3K/Akt-1 pathway., Overexpression of PIK3CA was confirmed in biopsy washout specimens and in postoperative tissues of papillary thyroid carcinoma, in comparison to macroscopically unchanged thyroid tissue, Allele-specific qPCR assays for the most frequent activating mutations in EGFR, KRAS, BRAF and PIK3CA in tumor-positive fine needle cytological aspirates were compared against histological material of primary tumors., Single nucleotide polymorphisms in PI3K gene is not associated with colorectal cancer., Data suggest that glioma cell survival occurs through a PI(3)-kinase/PDK1/PKC-iota/BAD mediated pathway., data indicated that colorectal cancers with KRAS and PIK3CA bi-mutations are more likely to develop into liver metastasis, Studies indicate that FoxOs have emerged as an important effector arm of PI3K/Akt signaling by driving multiple apoptotic gene expression., Data suggest that the PI3K/Akt signal transduction pathway is involved in the regulation and release of pro-inflammatory cytokines such as TNF-alpha and plays an important role in the development and progression of ulcerative colitis., CCL5 signaling induces GLI2 through a PI3K-AKT-IkappaBalpha-p65 pathway and requires GLI2 transcriptional activity to modulate IL-6 expression and Ig secretion in vitro and in vivo, These results suggest that ERalpha induces the down-regulation of PTEN through PI3K activation in breast cancer cells., controls inflammatory cytokine production in human neutrophils, Based on a comparative molecular analysis, we show that activated PIK3CA/AKT is a weaker inducer of cell senescence than is activated RAS., Data show that the Ras/PI3K/Akt pathway can account for Fyn over-expression in cancers., A detachment-induced and PI3K/Akt-mediated resistance to apoptotic effects of TRAIL, is demonstrated., The PIK3CA H1047R oncogene targets a multipotent progenitor cell and, furthermore, show that this model recapitulates features of human breast tumors with PIK3CA H1047R., PIK3CA mutations were detected in 19 (40%) of primary tumors and 21 (42%) of metastases, Data show that hepatocyte growth factor inhibits anoikis of pancreatic carcinoma cells through phosphatidylinositol 3-kinase pathway in which activation of Akt may be involved., Moreover, sustained PI3K/Akt signalling in Aspergillus fumigatus infected cells is an important determinant to resist apoptosis., PIK3CA amplification was frequently found in NSCLC, PIK3CA somatic mutations occurred in 39 (19.9%) of 196 endometrial carcinomas. No PIK3CA mutations were found in endometrial hyperplasias. PIK3CA amplification was observed in 24 (12.2%) carcinomas and in 2 (10%) hyperplasias., Inhibition of PI3K reduced rhTRAIL sensitivity independently of the cell line preference for either DR4- or DR5-mediated apoptosis signaling., Findings show that the oncogenic PI3K/Akt signalling pathway participates in maintaining cells in a type II phenotype by excluding CD95 from lipid rafts., Prediction of CH5132799 response on the basis of PIK3CA mutations could enable patient stratification in clinical settings., PIK3CA activating mutations and and PTEN loss is associated with less efficacy of trastuzumab therapy in metastatic breast cancer, These studies validate the Kit L575P-activated model of melanoma and establish the PI3K pathway as a dominant signaling pathway downstream of Kit in melanoma., Demonstrate the presence of PIK3CA and AKT1(E17K) mutations from pre-invasive to invasive to metastatic breast cancer tissue., Data show that PI3K dependent phosphorylation of Fbw7 stimulates its ability to ubiquitinate and degrade its substrates., Retinal pigment epithelial disruption induced by high glucose plus IL-1beta is prevented by erythropoietin through the downstream signaling of JAK2 and PI3K/AKT pathways., Tannerella forsythia epithelial cell entry is dependent on host PI3K signalling, purified BspA protein causes activation of this lipid kinase, and also requires the cooperation of host Rac1 GTPase., Results identify unique sites of PTEN and Akt regulation by means of S-nitrosylation, resulting in an "on-off" pattern of control of Akt/PI3K signaling., patients with Non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue that are positive for both PIK3CA and FOXP1 had a worse overall and progression-free survival, The present data indicate that activation of the PI3-kinase/PKB/AKT pathway through PIK3CA regulates various transformed phenotypes as well as growth and differentiation of HPV-immortalized cells, Investigated PIK3CA mutation in Chinese hepatocellular carcinoma patients.Exons 9 and 20 mutations of PIK3CA gene were detected.Two point mutations in exon 9 were found in only one patient (1/90; 1.11%), no mutation was found in exon 20 in any cases., Studies indicate that PI3K can phosphorylate and convert phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3) that leads to activation of AKT., PIK3CA mutations occur more often in elderly HER2-positive breast cancer patients. Most mutations were at H1947R & E542K. PI3K pathway activation resulting from PIK3CA mutations may lead to drug resistance to lapatinib & trastuzumab., Data suggest that PI3K and PKC are along the same pathway that branches into two separate ones involving each either p38MAP kinase or MEK/ERK., PI3K signaling via p110alpha regulates invadopodia-mediated invasion of breast cancer cells., Beclin1/PI3K-mediated autophagy prevents hypoxia-induced apoptosis in EAhy926 cell line, TGF-beta1 undergo a switch into mesenchymal cells and PI3K/Akt and MAPK/Erk1/2 signaling pathways serve to regulate TGF-beta1-induced epithelial-to-mesenchymal transition of A549 cells., Results indicate that stimulation of the early metastatic steps of motility and invasion by ErbB3 requires activation of the PI3-kinase pathway by the ErbB3 receptor., These findings provide evidence that mutations of the PIK3CA gene occur in the putative precursor lesions of ovarian clear cell adenocarcinoma, This paper reports the first purification of a phosphoinositide 3-kinase and shows that the protein is a heterodimer of an 85 kd regulatory subunit that mediates binding to phosphorylated proteins and a 110 kd catalytic subunit., Glycosaminoglycans and glucose prevent apoptosis in 4-methylumbelliferone-treated human aortic smooth muscle cells in a process mediated by Toll-like receptor 4, CD44, and PI3K but not by ERK1/2, These findings indicate that the expression of IL-15 up-regulated by IL-6 is associated with MAPKs-ERK1/2 and PI3K-AKT signaling pathways in HaCaT cells., Cells transformed by the p110alpha-H1047R mutant of PI3K show increased tyrosine phosphorylation of Stat3., results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in myelodysplastic syndrome patients., Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms., data confirm that PIK3CA is important to oral squamous cell carcinoma (OSCC) tumorigenesis and can contribute to oncogene activation of the PIK3CA/AKT pathway in OSCC, PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers., PIK3CA mutation in exon 20 is a negative prognostic factor in stage III colon cancer patients. Moreover, this negative effect is not present in stage I and II patients., Down-regulation of JAK1 by RNA interference inhibits growth of the lung cancer cell line A549 and interferes with the PI3K/mTOR pathway, CREG plays a critical role in protecting the vascular endothelium from apoptosis, and the protective effort of CREG against ECs apoptosis is through the activation of the VEGF/PI3K/AKT signaling pathway, FGF2 and EGF affect the motor neuron fate decision in human fetal neural stem cells differently through a fine tuning of the PI3K/AKT/GSK3beta pathway., The OHCI induces mitochondrial oxidative stress, leading to DNA double-strand breaks and elicitation of a phosphoinositol 3-kinase-mediated cellular response in peripheral blood lymphocytes., Accumulation of viral RNA in cells infected with influenza A or B viruses results in PI3K activation., Results demonstrate a PIK3CA mutation simultaneously occuring with a 15-up deletion in KIT exon 11 in gastrointestinal stromal tumors., PIK3CA mutations were uncommonly, but exclusively, seen in tubulovillous adenomas (4/124, 3.2%) and 1/4 (25.0%) tubulovillous adenomas with a focus of cancer, PI3 kinase-alpha/gamma-mediated signaling downstream of VEGFR2 activation regulated Akt-dependent survival signals, but it was not required to activate endothelial nitric oxide synthase or to elicit NO production in glomerular endothelial cells., Mutations in PIK3CA were found in 3 of 11 Intraductal tubulopapillary pancreatic neoplasms but not in intraductal papillary pancreatic mucinous neoplasms, These findings, representing the first genomewide search for variants influencing human protein phosphorylation, provide useful information about the PI3K/AKT/mTOR pathway., FASN inhibition not only abrogates lipogenesis, which is indispensable for cancer growth, but also downregulates oncogenic PI3K signaling., Data show that siRNA mediated targeting of PIK3CA may specifically knockdown the expression of PIK3CA in gastric cancer cells, providing a potential implication for therapy of gastric cancer., Survival, proliferation, leptin production, OB-R isoforms (OB-Ra and OB-Rb), phosphoinositide 3-kinase (PI3k) and BCL-2 expression have been tested after 24h, 48h and 72h of treatment with alpha-linolenic acid., Findings suggest that large HBsAg (LHBs) promotes tumorigenesis of hepatoma cells by triggering a PKCalpha/Raf1 to Src/PI3K/Akt signaling pathway, revealing novel insights into the underlying mechanisms of HBV-associated hepatocarcinogenesis., A frequent PIK3CA mutation appears in a series of rosette-forming glioneuronal tumors., multiple mutations were identified in phosphoinositide-3-kinase (PI3K), catalytic, alpha polypeptide (PIK3CA) (H1047R, E-->lysine at codon 545 [E545K], and H-->proline at codon 701 [H701P]) that were not observed previously in osteosarcoma, activating mutation of PIK3CA, loss of PTEN, or IGF1R expression have a role in round cell transformation, The overall prevalence of PIK3CA mutations was 23% (7/31) for both tumor types (22% in glioblastoma multiform, and 25% in anaplastic astrocytoma)., Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer, the activation of PI3K and MEK pathways is not the only mechanism of EGFR-resistance, PIK3CA exon 20 mutations may be a potential biomarker for resistance to anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer. [Review and meta-analysis], Addition of short (6 to 16 amino acids) peptide sequences to the N-terminus of p110alpha induces a gain of function includeds signaling, oncogenic transformation and stimulation of cell growth., PIK3R1, like PIK3CA, is a potential therapeutic target in Glioblastoma multiforme and that it also influences tumor cell growth and motility, In endometriotic stromal cells, overactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway contributes to the reduced expression of the decidua-specific gene, IGFBP1, potentially through reduced levels of nuclear FOXO1., combination of low CEN7 copy number, PTEN loss, and PI3KCA gain may be useful for identifying NSCLC patients unlikely to benefit from treatment with EGFR (TKIs), specifically in wild-type EGFR cases, Proliferation of human IVD cells is regulated by exogenous and autocrine growth factors mainly via the MEK/ERK and PI-3K/Akt pathways., The prognostic impact of Akt (Akt1) phosphorylated at threonine308 and serine473, Akt2, Akt3, PI3K and PTEN, alone and in coexpression with ER and PgR in non-gastrointestinal stromal tumor soft tissue sarcomas., PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma., Data indicate that PIK3CA mutations occur in lung adenocarcinomas, usually concurrently with EGFR, KRAS, and anaplastic lymphoma kinase (ALK)., BDNF promotes EGF-induced proliferation and migration of neural stem/progenitor cells through the PI3K/Akt pathway., PIK3CA rs6443624 and rs9838411 variants either somewhat or significantly decreased risk of endometrial cancer in a dominant model., Loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development and frequently coexists (not mutually exclusive) with PIK3CA mutations., Breast cnacer patients with PIK3CA mutations or increased PI3K pathway activity had a significantly poorer survival despite adequate treatment with adjuvant chemotherapy and trastuzumab., Data suggest that wild-type PTEN gene transfection might increase drug sensitivity or reverse drug resistance via inhibiting the PI3K/Akt pathway and regulating downstream molecules of the cell signaling transduction pathway in K562/ADM cells., Mutations in ras PIK3CA are present in benign lichenoid keratosis., Data indicate that NVP-BKM120 inhibits all four class I PI3K isoforms in biochemical assays., Gene mutations of PIK3CA are not associated with the postoperative prognosis of patients with hepatocellular carcinoma., Results show a novel anti-inflammatory role for the PI3K/Akt signaling pathway in microglia, and show that Ad-IRF3 suppressed proinflammatory genes and enhanced anti-inflammatory genes., PIK3CA mutation status was analyzed by sequencing in 94 tumors. phosphatidylinositol 3'-kinase pathway alteration might have a favorable prognostic impact on endometrial cancers in Chinese women., conclude that exocrine pancreatic expression of phosphatidylinositol 3-kinase p85alpha subunit is attenuated by aging, Although PIK3CA mutation has been found in 10-18% of colorectal cancer patients, the results are still inconclusve if it affects the efficacy of cetuximab or panitumumab.[review], Results describe how phosphatidylinositol 3-kinase and protein kinase D1 cooperate to regulate the insulin-like growth factor signaling pathway., Mutational activation of both BRAF and PIK3CA genes does contribute to hepatocellular tumorigenesis at somatic level in Southern Italian population., Patients with PIK3CA mutations treated with PI3K/AKT/mTOR inhibitors demonstrated a higher response rate than patients without mutations., loss of PTEN expression (by immunohistochemistry) and PIK3CA mutation is likely to be predictive of a lack of benefit to anti-EGFR therapy in metastatic colorectal cancer, UCA1 regulated cell cycle through CREB via PI3K-AKT dependent pathway in bladder cancer., PIK3CA mutation is associated with colorectal serrated adenocarcinoma., data suggest that lamin A/C proteins are positively involved in malignant behavior of PC cells through the PI3K/AKT/PTEN pathway. Lamin A/C may represent a new oncogenic factor and a novel therapeutic target for PC, These findings strengthen the evidence for involvement of the Notch, Hedgehog, NF-KB, and PIK3CA pathways in breast cancer development, and point to novel processes that likely are involved., PIK3CA mutations confer constitutive activation of PI3K, which initiates intracellular kinase signaling cascades that promote cell proliferation and survival., PIK3CA mutations may play an important role in the carcinogenesis and development of breast cancer., PIK3CA mutation was associated with significantly longer metastasis-free survival in breast cancer patients., PIK3CA mutations at exon 9 or 20 may have different impact on the prognosis in endometrial carcinoma., PI3K/mTOR inhibitors can enhance 5-FU cytotoxicity in vitro and in vivo, especially in PIK3CA mutant tumor cells., Studies suggest that the effects of PHLPP1 deletion on prostate carcinogenesis may be explained by the strong dependence of prostate cancer on phosphoinositide 3-kinase (PI3K)/Akt signalling., Data indicate that the mechanisms of action of ON 01910.Na invloved PI3K/AKT inhibition and induction of oxidative stress response., High p110alpha is associated with non-small cell lung cancer., coexistence of PIK3CA (the PI3K p110alpha subunit) exon 9 and 20 mutations, but not PIK3CA mutation in either exon 9 or 20 alone, is associated with poor prognosis of colorectal cancer patients, The relationship between expression and genetic alterations of the components of the PI3K/AKT pathway in non-small cell lung cancer, was investigated., Merkel cell carcinoma samples were analyzed for activating PIK3CA and AKT1 mutations., analysis of FGFR2 point mutations in 466 endometrioid endometrial tumors and their relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations, we have analyzed the prevalence of somatic mutations in the FGFR3, PIK3CA, AKT1, KRAS, HRAS, and BRAF genes in bladder cancers, The PIK3CA mutation rate was lower in adenocarcinomas compared to other forms of lung cancers, Our findings indicate that the effects of mutant PIK3CA are both cell type- and mutation-specific., PIK3CA mutations were identified in 13/24 columnar cell lesions (54%) and 3/8 invasive carcinomas (37%)., Data indicate a functional link between the Notch1 and PI3K/Akt pathways in clear cell renal cell carcinoma (CCRCC)., This review outlines the interaction of the PI3K pathway with other signaling cascades, highlights mechanisms involved in hyperactivation, discusses current therapeutics in cancer-related clinical trials that target this pathway., The PI3K/AKT pathway can be an important signaling pathway for the survival of BRCA1-defective breast cancer cells., Both osteopontin-c and osteopontin-b splic-ing isoforms promote distinct aspects of PCa progression by inducing PI3K signaling., A PIK3CA mutation was observed in 16 (17%) specimens in patients with endometrial cancer., In summary, the PI3K/PKCiota regulates the alternative splicing of Bcl-x pre-mRNA with implications in the cell survival of NSCLC cells., Aberrant DLC1 methylation and PIK3CA mutat-ions may have important roles in extra-mammary Paget's disease pathogenesis., findings describe a PI3K-driven, NF-kappaB-dependent transcriptional profile that may play a critical role in promoting a microenvironment amenable to tumor progression, In human airway smooth muscle cells, regulation of CD38 expression occurs by specific class I PI3K isoforms., Although there is an association of PI3 kinase signaling and chemoresistance in advanced ovarian cancer, there is no clear evidence that this is driven specifically by PIK3CA mutations., We further identify the activation of the PI3K/AKT signal pathway by T3 as an underlying mechanism for the enhanced conversion to cell pluripotency in this model., KRAS, BRAF, and PIK3CA mutations in colorectal cancer have sustained prevalence rate in the Taiwanese population., In the present study, we did not find any significant correlations between KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression and various clinicopathological features in Chinese patients with colorectal cancer., Data suggest that phosphoinositide-3-kinase/Akt and mammalian target of rapamycin (mTOR) pathway signaling differentially regulate phospho-Mst1-Thr-120/Thr-183., Our findings implicate amplifications of 3q26 focused on PIK3CA and 8q24 focused on MYC in chronic lymphocytic leukemia., Single nucleotide polymorphism in PIK3CA is associated with synchronous endometrial and ovarian cancer., Breast cancer patients with tumors harboring a PIK3CA mutation have a better clinical outcome than those with a wild-type PIK3CA gene., Angiosarcoma (AS) is characterized by a complex pattern of alterations of the TP53 and PIK3CA/AKT/mTOR pathways that does not depend on MYC amplification status., In conclusion, SPRY2 is an important tumour suppressor in prostate cancer since its loss drives the PI3K/AKT pathway via functional interaction with the ErbB system., CLOVES syndrome is caused by postzygotic activating mutations in PIK3CA, Our data highlights a new functional synergism between oncogenic EGFR and PIK3CA with WNT/beta-catenin conferring high tolerance to oxidative stress generated by nutrient deprivation., KRAS and PIK3CA mutations frequently coexist in patients with colorectal cancer, and are associated with clinical characteristics and outcome., The interaction between HGF and c-Met increases OPN expression in human osteoblasts via the PI3K, Akt, c-Src, c-Jun, and AP-1 signaling pathway., several Rho family small GTPases activate PI3K by an indirect cooperative positive feedback that required a combination of Rac, CDC42, and RhoG small GTPase activities, PIK3CA H1074R mutation and PTEN loss differentially regulate LIM-kinase1 and slingshot-1L., Cyclic hydrodynamic pressure stimulating the roliferation of human bladder smooth muscle cells cultured in scaffolds. The signal transduction mechanism for this process is involved with the PI3K/SGK1 and not the PI3K/AKT signaling pathway., PIK3CA mutations were significantly associated with a favorable overall survival of patients with ovarian clear cell carcinoma, Mucinous breast carcinomas lack PIK3CA mutations., Using high throughput mutation screening platform, we identified that PIK3CA mutations were the most frequently observed target for gastric adenocarcinoma., Sequencing of PIK3CA in ten individuals with fibroadipose hyperplasia syndromes identified either the p.His1047Leu alteration or a second cancer-associated alteration, p.His1047Arg, in nine cases., Exome sequencing and mass spectrometry analysis in paired brain-blood samples from individuals with hemimegalencephaly (20 cases) identified de novo somatic mutations in 30% of affected individuals in the PIK3CA, AKT3 and MTOR genes., identified mutations in AKT3, PIK3R2 and PIK3CA in 11 unrelated families with megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndromes, A high copy number of MET or PIK3CA was found to be associated with poorer prognostic features and triple receptor-negative disease, analysis of multiorgan metastasis of human HER-2+ breast cancer in Rag2-/-;Il2rg-/- mice and treatment with PI3K inhibitor, this study evaluated whether activating mutations of PI3KCA or complete loss of PTEN is associated with response to anti-human Her2 treatment in breast cancer, Epithelial CEACAMs associate in cis with other membrane receptor(s) via their extracellular domains to trigger bacterial uptake in a PI3K-dependent manner., These data support a strong biological-link between NFkB and the PI3-kinase/AKT pathway in the modulation of anti-apoptotic effects in primary effusion lymphoma cells., study demonstrated that the somatic mutations of PIK3CA and JAK2 occurred in a small fraction of sarcomas and that these mutations may not play a principal role in the development of sarcomas, This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in this tumorigenic process., In CRC patients treated with cetuximab, activating mutation signatures for PIK3CA (49 genes) were developed., PIK3CA-targeted short hairpin RNAs can block the phosphoinositide 3-kinase-Akt signaling pathway and inhibit cell growth, increase apoptosis, and induce cell cycle arrest in PIK3CA-mutant colon cancer SW948 cells, Data provide information for developing new therapeutics targeting PI3K/Akt/mTOR signaling pathway in autoimmune diseases like psoriasis and rheumatoid arthritis., Electroacupuncture profoundly activated PI3K/Akt signaling in ischemic cerebral tissues., PI3K expression and PIK3CA mutations are related to colorectal cancer metastases, LOX-1 up-regulation induced by AGE-BSA was a receptor mediated through RAGE and is via the PI3K/PDK1/mTORC2 pathway, High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide-3-kinase and BRAF mutations., Data suggest that targeting Hedgehog (Hh) pathway alone or in combination with PI3K/AKT pathway could be a novel therapeutic option in treating endocrine-resistant breast cancer., The Epstein-Barr virus protein LMP1, which lacks the canonical ITAM required for Syk activation, can nevertheless activate Syk, and the Src kinase Fyn, resulting in downstream c-Cbl and PI3K/Akt activation., Deregulated c-MYC and PI3K activity cooperate in Burkitt lymphoma pathogenesis., These results demonstrated that hepatitis B virus X protein could upregulate LASP-1 through PI3-K pathway to promote the proliferation and migration of hepatoma cells., Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway, Data indicate that mutation frequency in malanoma patients was found witih BRAF(V600) in 51%, NRAS in 19%, PI3K pathway in 41% and PTEN in 22%., Molecular genetic aberrations involving the p53, cyclin E-FBXW7, and PI3K pathways represent major mechanisms in the development of uterine serous carcinoma., Class IA phosphatidylinositol 3-kinase p110alpha is required for vacuole maturation, heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population., Data indicate that resveratrol suppressed IL-1beta-induced activation of NF-kappaB and PI3K in a dose- and time-dependent manner., Data indicate that KRAS, BRAF, PIK3CA, and AKT1 mutations can be rapidly and accurately detected for cancer diagnosis., these results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA., results suggest that PIK3CA gene mutations may play a key role in tumourigenesis and aggressiveness of bronchopulmonary neuroendocrine tumours, diverse PIK3CA mutations stimulate lipid kinase activity by facilitating allosteric motions required for catalysis on membranes, The subgroup of ovarian clear cell carcinomas harboring activated PIK3CA seems to have better prognosis possibly due to more indolent biological property compared to tumors without PIK3CA activation., Results indicate that CIB1 is uniquely positioned to regulate PI3K/AKT and MEK/ERK signaling and that simultaneous disruption of these pathways synergistically induces a nuclear GAPDH-dependent cell death., the Ras-PI3K signaling pathway targets specific epigenetic modifications in tumor cells, PI3K has a crucial role in regulating Brn-2 and Pax3 expression and neoplasm invasiveness, and it is a key determinant of melanoma subpopulation diversity., Data indicate that copy number amplification of the PIK3CA gene is associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients without lymph node metastasis., LY294002 prevented phosphorylation of protein kinase B (PKB/Akt) by inhibition of PI3K phosphorylation activity., Investigated PIK3CA mutations in ILBC with special reference to late stage tumor progression. PIK3CA mutations were detected in 32/88 (36%) specimens., PI3K is a mediator of stretch-induced COX-2 expression in urothelial cells., PIK3CA mutation is associated with early-stage low-grade endometrial cancers., EGFR and downstream genetic alterations in KRAS/BRAF and PI3K/AKT pathways have roles in colorectal cancer and treatment [review], PIK3CA mutations lead to a shift towards a highly glycolytic phenotype., p110alpha was activated at mitosis entry and regulated early mitotic events, such as PIP(3) generation, prometaphase progression, and spindle orientation., Src family kinases, PI3 kinase and protein kinase C synergize to mediate Gq-dependent platelet activation, PIK3CA H1047R mutation was the only independent factor predicting response to PI3K/AKT/mTOR inhibitors in patients with advanced cancers, Data indicate that resistance to UVB induced apoptosis in the alpha6 integrin(high+)/CD44(+) cells involved increased expression of TAp63 and was overcome by PI-3 kinase inhibition., PI3K/Akt signaling is utilized by alphaIIb-mediated outside-in signaling to activate platelets., either mutant PIK3CA expression or PTEN loss, but not mutant AKT1 E17K, cause disrupted epithelial architecture., activation of the PI3K-AKT pathway through loss of PTEN or PIK3CA mutation was frequently observed in trastuzumab refractory breast cancer., Use of aspirin after diagnosis was associated with longer survival among patients with mutated-PIK3CA colorectal cancer. Suggests that the PIK3CA mutation in colorectal cancer may serve as a predictive molecular biomarker for adjuvant aspirin therapy., identified somatic gain-of-function mutations in PIK3CA in the affected nerve that caused macrodactylous overgrowth, PI3K/AKT/mTOR signalling components appear to be differentially implicated in urothelial tumorigenesis and, with the exception of p85aPI3K, are unrelated to the PIK3CA or AKT1 mutational status., Data indicate that cells grown in three-dimensional (3D) gels showed reduced proliferation and migration as well as reduced PI3K pathway activation when compared to cells grown in 2D., In the present study, the authors provide evidence that the West Nile virus capsid protein blocks apoptosis through a phosphatidylinositol (PI) 3-kinase-dependent pathway., One hundred and ten patients (51%) were identified who were potentially nonresponders to anti-EGFR therapy, PIK3CA amplification was detected in thirty-seven percent of lung squamous tumors and five percent of lung adenocarcinomas., Molecular characterization of single CTCs demonstrated considerable intra- and interpatient heterogeneity of EGFR expression and genetic alterations in EGFR, KRAS, and PIK3CA, Targeting the phosphoinositide 3-kinase p110-alpha isoform impairs cell proliferation, survival, and tumor growth in small cell lung cancer., Data show that a photodynamic therapy (PDT) dose-dependent upregulation of CRP gene, as well as of PTX3 and ficolin 1 genes in lung tumor A549 cells, and indicate critical role played by PI3K/Akt/AP-1 pathway., Our finding that PIK3CA exon 20 mutations were associated with more aggressive breast cancer and poor outcomes, regardless of the treatment regimen, has important clinical implications., A dramatically lower prevalence of the heterozygous genotype G/T at rs17849071 of PIK3CA was found in patients with follicular thyroid cancer., In conclusion, authors have found that the varicella-zoster virus ORF12 protein activates the PI3K/Akt pathway to regulate cell cycle progression., in primary endometrial carcinoma, mutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status; PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients, Mutations affecting BRAF, EGFR, PIK3CA, and KRAS are not associated with sporadic vestibular schwannomas., miR-148b controls malignancy by coordinating a novel pathway involving over 130 genes and, in particular, it directly targets players of the integrin signaling, such as ITGA5, ROCK1, PIK3CA/p110alpha, and NRAS, as well as CSF1, Findings indicate driver mutations in AKT1, and extend the number and type of mutations that activate the PI3-kinase pathway in human breast cancers., Findings suggest that inhibiton of Bcl-2, Bcl-xL and PI3K, and release of Bim from Bcl-2/Bcl-xL and GSK3alpha/beta culminating in Bax/Bak activation and apoptosis., 8 of 91 (8.8%) unrelated CS individuals without germline PTEN mutations carried 10 germline PIK3CA mutations, PIK3CA mutations in diverse cancers were not associated with clinical characteristics, but were correlated with MAPK mutations. PIK3CA mutations, especially, H1047R, were associated with attaining a PR/CR to PI3K/AKT/mTOR pathway inhibitors., Linoleic acid induces opening of connexin26 hemichannels through a PI3K/Akt/Ca(2+)-dependent pathway, In cervical cancer patients treated with CRT, tumor PIK3CA mutation status was associated with overall survival in FIGO stage IB/II cervix cancers., Coincided with the activation of the PI3K/AKT pathway., Selective inhibition of phosphoinositide 3-kinase p110alpha preserves lymphocyte function, Data indicate protein secretion pathways activated by monosodium urate (MSU) in macrophages, and reveal a novel role for cathepsin B and Src, Pyk2, PI3 kinases in the activation of unconventional protein secretion., FGFR2, KRAS and PIK3CA are frequently mutated in primary and metastatic endometrial lesions., PIK3CA has a role in response to everolimus and letrozole in estrogen receptor positive breast cancer, No correlation was observed between PIK3CA exon 9 and 20 mutations and age at breast cancer diagnosis, histological type, hormone receptor and HER2 status., Data indicate that phosphatidylinositol 3'-kinase (PI3K) alpha and beta p110 isoforms of PI3K are broadly expressed in myeloma., PIK3CA amplifications in large cell and squamous cell carcinomas were significantly higher compared with adenocarcinomas., High PIK3CA/PIK3CD ratio identified a subset of primary mantle cell lymphomas resistant to GS-1101 and this ratio increased significantly with relapse., Results indicate a key role of class I PI3K in IL-2R endocytosis that creates a link with IL-2 signalling., The rate of PIK3CA mutations in this series of micropapillary carcinomas is similar to invasive ductal carcinomas; however, there may be an enrichment of AKT1 mutations., only 5 tumours with exon 20 PIK3CA mutations were detected. Only PIK3CA mutations occasionally coexisted with other gene mutations in colorectal cancer., PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression., 14-3-3 negatively regulates the RGC downstream of the PI3-kinase/Akt signaling pathway, PIK3CA mutations are associated with lung cancer., PIK3CA-mutant lung cancers are dependent on this driver oncogene, whereas in other patient cases, the mutation may modulate the effect of another oncogenic process., down regulation of fibroblast growth factor receptor 3 (FGFR3) and PI3K/Akt signaling mechanisms leading to inhibition of cell proliferation and induction of molecular mechanisms of apopto, Studies suggest that adipokines, AMPK, PI3K and the PPAR signaling pathways could be targets of therapeutic strategies for the ovarian cancers and reproductive pathologies., Results indicate that the induction of MCP-2/CCL8 by mycobacteria is dependent on the activation of TLR2/PI3K/Akt signaling pathway., The correlation between T stage of gastric cancer and the higher expression of CD40, VEGF, AKT, and PI3K, along with lower S100 expression in DC, may provide insights into future targets for more effective immunotherapy for cancer., PIK3CA mutation is a promising predictive biomarker for poor survival in mCRC patients treated with anti-EGFR mAbs, particularly in KRAS wild-type patients., cell-autonomous phosphoinositide 3-kinase and 3-phosphoinositide-dependent protein kinase 1 are key effectors of oncogenic Kras in the pancreas, mediating cell plasticity, acinar-to-ductal metaplasia, and pancreatic ductal adenocarcinoma formation, these data suggest the efficacy of agents that target the MAPK and PI3K pathways can be improved by combination with a Bcl-2 family inhibitor., PI3K is involved in CKII inhibition-mediated cellular senescence in HCT116 cells., PIK3CA mutations in esophageal squamous cell carcinoma are associated with longer survival., High phospho-stathmin(S38) is associated with PI3K pathway alterations, Data suggest that 17 beta-estradiol enhances the the glucose uptake, activates PI3K/Akt signaling pathway, leading to translocation of glucose transporter 4 to the plasma membrane in an ERalpha-dependent manner., About one fourth of mCRC cases wild-type for KRAS codons 12 and 13 present other mutations either in KRAS, BRAF, or PIK3CA, many of which may explain the lack of response to anti-EGFR therapy observed in a significant proportion of these patients., Data indicate that concurrent BRAF and PI3K/mTOR blockade results in induction of apoptosis., APG dramatically reduced Nrf2 expression at both the messenger RNA and protein levels through downregulation of PI3K/Akt pathway., PIK3CA mutations are not associated with tyrosine kinase inhibitors treatment efficacy in non-small cell lung cancer., p110alpha acts as a negative regulator of beta cell exocytosis and insulin secretion, while p110beta is a positive regulator of insulin secretion through a mechanism separate from its catalytic activity, Data show that somatic cell knockin of both KRAS G12V and oncogenic PIK3CA mutations in human breast epithelial cells results in cooperative activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways., mutational analysis of TP53 (exons 4-9) and CTNNB1 (exon 3) as well as PIK3CA (exon 9) genes in hepatocellular carcinoma from Southern Italy, PI3K signaling contributed to tumor growth and vasculogenic mimicry of gallbladder carcinomas., PIK3CA mutation status was also not associated with treatment outcome after first-line tamoxifen, the review provides a complete picture of the PIK3CA oncogene and its deregulation in oral cancer (Review), These results confirm that the outcome of HER2-positive patients treated with trastuzumab is significantly worse in patients with PIK3CA-mutated compared with wild-type tumours., Results show that stromal cell-derived factor-1 (SDF-1) enhanced ovarian cancer cell invasion through alphavbeta6 integrin-mediated urokinase-type plasminogen activator (uPA) expression via the p38 MAPK and PI3 K/Akt pathway., Data indicate that the PI3K/Akt pathway plays an important role in the regulation of telomerase reverse transcriptase (hTERT) activity in response to histone deacetylases (HDACs) inhibitor., Results indicate that ADAM17 is upregulated by hypoxia and contributes to hypoxia-induced cisplatin resistance via EGFR/PI3K/Akt pathway., the PI3K/AKT/mTOR signaling pathway, which was overactivated in APA and IHA compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of PA., PIK3CA exon 20 and PTEN mutations associated with features of colon cancer tumorigenesis, our results suggest that CAPE suppresses phosphoinositide 3-kinase/AKT/XIAP pathway leading to apoptosis in melanoma tumor cells in vitro and in vivo, Disruption of the IRS1-p110alpha E545K interaction destabilizes the p110alpha protein, reduces AKT phosphorylation, and slows xenograft tumor growth of a cancer cell line expressing p110alpha E545K., Aberrations in PIK3CA and PTEN did not add significant prognostic information on colorectal carcinoma patients., These results reveal a previously unknown, essential role of PI3K in the life cycle of human astrovirus type 1., Report a synthetic lethal interaction between PI3K/mTOR and MEK inhibitors in rhabdomyosarcoma., Mitotic Plk1 activity is regulated not only by Plk1-Thr210 phosphorylation, but also by Plk1 binding to 14-3-3gamma following Plk1-Ser99 phosphorylation downstream of the PI3K-Akt signalling pathway., Loss of ARID1A expression, PI3K-Akt pathway alterations, TP53 status and microsatellite instability are involved in endometrial cancer., Effectively inhibited the PI3K signaling pathway., no specific relationship between mutation in the exon of PIK3CA and clinical characteristics of the hepatocellular carcinoma in korean patients, Data indicate that NVP-BKM120 inhibited pan-class I phosphatidyl-inositol-3-kinase and decreased cell proliferation and increased apoptotic cell death in diffuse large B-cell lymphoma (DLBCL)., A downregulation of FASN effectively inhibits the activity of "HER2-PI3K/Akt axis" and alters the malignant phenotype in colorectal cancer cells., We also examined 61 of our cases for the presence of PIK3CA, AKT1, PTEN and K-RAS mutations., PIK3CA-mutated colorectal cancer appears to have a distinct epidemiologic profile that is of clinical significance., Data indicate that the activation of MAPK and PI3K pathways resulted in TGF-beta1 signaling by down-regulating Nm23-H1 expression and up-regulating the expression of TbetaRI and TbetaRII, favoring further activation of multiple signaling pathways., PIK3CA mutations were associated with a better outcome, however this effect disappeared after 3 years. There were no statistically significant associations with trastuzumab benefit., The PI3K/Akt inhibitor LY294002 can enhance chemosensitivity of human gastric cancer to VCR., PIK3CA mutation also contributes to significantly decreased survival for patients with wild-type BRAF tumors., 4 of 41 HPV-negative tumors (10%) demonstrated PIK3CA hot spot mutations, 3 at codon 1047 and 1 at codon 542. Of 46 HPV-positive tumors, 13 (28%) demonstrated activating PIK3CA mutations, including 7 at codon 542, 5 at codon 545, and 1 at codon 1047., These results suggest that the phosphatidylinositol 3-kinase/Akt signaling pathway plays an important role in beta1 integrin-mediated internalization of Staphylococcus aureus by alveolar epithelial cells., Activation of the PI3K/Akt pathway with expression of survivin identified a subgroup of acute myeloid leukemia patients with an excellent outcome., PIK3CA mutation and copy number gain were detected in 3 (4.9%) and 8 (13.1%), respectively, of 61 gastric cancer samples while PTEN loss was detected in 24 (39%) of the tumours. Two tumours had both PTEN loss and PIK3CA copy number gain., This study investigated the impact of KRAS, NRAS, BRAF, PI3KCA and TP53 status on outcome of elderly metastatic colorectal cancer patients, Data indicate that increased activation of PI3K/AKT signaling was observed in the cholangiocarcinoma (CCA) tissues, and suggest that inhibition of PI3K and mTOR activity by the inhibitor NVP-BEZ235 has anti-cancer activity against CCA., PIK3CA mutations and/or PTEN loss were identified in the wide morphologic spectrum of salivary duct carcinomas., frequent PIK3CA mutations in patients with high-risk HNSCC confined predominantly to the oropharyngeal and sinonasal subsites; for the first time, mutation in AKT1 has been identified in HNSCC, we discuss the preclinical and clinical experience with the rapalogues in RCC, potential mechanisms of resistance to the rapalogues, and the progress in the clinical development of novel agents directed against the phosphatidylinositol 3-kinase/Akt/mTOR, This study shows that PI3K inhibitors only transiently inhibit AKT which limits their antitumor activities., Among 30 breast tumors, 10(33%) had BCSCs with AKT1, HRAS, or PIK3CA mutations. 3 mutations were detected in PIK3CA.Tumors in which BCSCs have defects in PI3K/Akt signaling are significantly more likely to manifest nodal metastases., Increase in the expression of PI3K was associated with colorectal carcinoma., our findings suggest that loss of CDKN2A and, to a lesser extent, KRAS and PIK3CA somatic mutations have a role in the progression of a benign to an atypical proliferative Brenner tumor, AKT1 E17K is a bona fide oncogene in a human luminal breast cancer context. Distinct PI3K pathway mutations confer differential sensitivity to drugs targeting the pathway at different points and by distinct mechanisms., Results suggest that IFN-gamma-mediated IL-27 protein but not IL-27p28 gene expression is positively regulated by the C-Jun N-terminal kinases (JNK), mitogen-activated protein kinases (MAPKs) and the phosphoinositide 3-kinase (PI3K)., Uterine serous carcinoma cell lines with oncogenic PIK3CA mutations were significantly more sensitive to GDC-0980 exposure., In PIK3CA-mutant cancer cell lines with persistent mTORC1 signaling, the addition of the allosteric mTORC1 inhibitor RAD001 to the cells along with BYL719 resulted in reversal of resistance in vitro and in vivo., Oncogenic mutations of p110alpha isoform of PI 3-kinase upregulate its protein kinase activity., PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male breast cancer., Data indicate that inflammatory cytokine-induced increases in chronic lymphocytic leukemia (CLL) cell adhesion to stromal cells are correlated with ZAP-70 expression and blocked by PI3K inhibitor., PIK3CA mutations are significantly associated with lower grade and hormone receptor positivity in Arab breast cancer patients., PI3K p85alpha-depletion results in activated expression of apoptosis-associated genes., Multivariate analyses revealed that PTEN expression (HR, 0.48; p = 0.02) and absence of PI3K expression (HR, 0.2; p = 0.001) were independent prognostic factors for increased PFS, Data indicate that PYK2 N-terminal domain interacting receptor 1 (Nir1) could induce epithelial-mesenchymal transition by stabilising Snail via the PI3K/Akt/GSK3beta/Snail signalling pathway through binding to CCL18., mutations in KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA detected in Asian patients were not predictive of clinical benefits from cetuximab treatment., PIK3CA gene mutations have been shown to predict a better otcome in ER/HER2 negative breast cancer, treated with endocrine therapy., Data indicate that dual targeted inhibitors of PI3K/mTOR in combination with inhibitors of RAS/ERK signalling as a potentially effective approach to treating ovarian cancer., PIK3CA mutation does not predict benefit from rofecoxib therapy, but it does predict reduced colorectal carcinoma recurrence in regular users of low-dose aspirin after diagnosis., suggesting that the changes in AKT/BCL2 signaling molecules might mediate growth and anti-apoptosis processes at least in part, thus increasing the survival potential of Congenital Giant Nevi melanocytes and maintaining their integrity, Some mutations in the gene encoding for the catalytic subunit of phosphatidyl-inositol-3-kinase, the PIK3CA gene, plays an important role, especially in the resistance to targeted therapies., Heavy metals in cigarette smoke induce PI3K expression in epithelial cells and tumor cells., Induced apoptosis mainly via the PI3K/AKT pathway., Its signal plays a crucial role in tumor genesis and tumor progression by promoting cell proliferation and inhibiting apoptosis., Phosphoinositide 3-kinase (PI3K) is required for PSGL-1-induced beta1 integrin clustering which ultimately regulates beta1 integrin-mediated Jurkat cell adhesion to fibronectin., PIK3CA gene mutations were found in 13 (16%), of 28 patients with squamous cell anal cancer, Results show PI3KCA mutations present in 34% of human breast cancer patients and significantly higher PIK3CA expression in breast cancer tissues in comparison with control tissues., In a Chinese cohort, rs7646409 genotype distributions between the osteosarcoma and control groups was significantly different (P = 0.032). Taking genotype TT as a reference, the risk of osteosarcoma increased three fold in patients with genotype CC., The frequently discordant genotypes of usual ductal hyperplasia/columnar cell change and concurrent carcinoma support a role for PIK3CA-activating point mutations in breast epithelial proliferation, perhaps more so than transformation., A screen of a cohort of radial scars for a large panel of activating point mutations, revealing PIK3CA mutations in over 60% of specimens., In chemotherapy-refractory colorectal cancer, neither PIK3CA mutation status nor PTEN expression were prognostic, nor were they predictive of benefit from cetuximab, PIK3CA mutations and PIK3R1 underexpression show opposite effects on patient outcome and could become useful prognostic and predictive factors in breast cancer., Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy., PI3KCA mutation was associated with the absence of Her2/neu amplification/overexpression and a low level of MIB1/Ki-67 labelling, PIK3CA gene hypomethylation plays a key role in the tumorigenesis and development of esophageal cancer in Chinese patients, while the mutations of PIK3CA gene have little effect on the development of esophageal cancer, Knockdown of RPS7 resulted in increased expression of P85alpha, P110alpha, and AKT2., This allows the usage of p110alpha-specific PI3K inhibitors and thus may spare patients the toxicities of pan-PI3K inhibition to allow maximal dosage and efficacy., PIK3CA exon 9 or exon 20 missense mutations were more commonly observed in cases that were deficient for mismatch repair protein expression (p=0.0058) and showed loss of ARID1A expression, Data iindicate that he combination therapy of mTOR inhibitor RAD001 and PI3K (phosphatidylinositol 3-kinase) inhibitor LY294002 decreased the cell growth in vitro and progression of liver metastasis in vivo., Findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling., Our study demonstrates relatively low frequency of PIK3CA mutations and amplifications in ovarian clear cell carcinoma., Dengue virus 2 subgenomic RNA induces apoptosis through the Bcl-2-mediated PI3k/Akt signaling pathway., The Pik3ca(H1047R) mutation promotes the development of highly aggressive and invasive adenocarcinomas in intestine., Data indicate that responses were noted in patients with HER2-amplified breast cancer resistant to trastuzumab, HER2-mutant non-small-cell lung cancer, and tumor types without identified mutations in the HER-PI3K-mTOR pathway., Data indicate that seven genes showed statistical enrichment for mutation, Low expression of miR-1 and high expression of PIK3CA are closely related to the invasion, progression and metastasis of non-small-cell lung cancer.There is a negative correlation between the expression of miR-1 and PIK3CA in non-small-cell lung cancer., PIK3CA mutations/amplification, HRAS mutation, or PTEN loss that likely lead to PI3K pathway activation were identified in 34 of 75 cases (45%) and did not correlate with disease specific survival., PIK3CA gene alteration in non-muscle invasive bladder tumors predicts reduced recurrence., blocking PI3K/Akt signaling pathway by LY294002 or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion has to, patients with PIK3CA-mutated tumors showed trend towards favorable overall survival (P = .085) but not disease-free survival (P = .238), suggesting that PIK3CA gene status may be favorable predictive marker in esophageal squamous cell carcinoma patients, This paper presents an overview of PIK3CA mutations in the path PI3K/PTEN/Akt of the most common cancers., PIK3CA mutations are associated with non--small-cell lung cancer., Affected tissue from individuals with facial infiltrating lipomatosis contains PIK3CA mutations that have previously been reported in cancers and in affected tissue from other nonheritable, overgrowth disorders., AFP can promote the proliferation of hepatoma cells via activation of PI3K/Akt signaling pathway., Data indicate that PI3K signaling pathway was critical for the anti-myeloma activity of BENC-511., Data indicate that siRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on Colorectal cancer (CRC) cell growth., PIK3CA mutations showed a trend toward an association with an increased risk of death compared to absence of those mutations in African American colorectal cancer patients., Te structure and function of the p110alpha enzyme and two of its most common oncogenic mutations. [Review], These results suggest that the combination of PI3K inhibition with dual HER2 blockade is necessary to circumvent the resistance to HER2 inhibitors conferred by PIK3CA mutation and also provides benefit to HER2+ tumors with wild-type PIK3CA tumors., this is the first reported case to our knowledge of a patient with both a possible germline EGFR T790M mutation and a somatic PIK3CA mutation., PIK3CA mutations do not have clinical validity to predict intrinsic resistance to adjuvant tamoxifen and may therefore be unsuitable as companion diagnostic for PI3K/AKT/mTOR inhibitors in ERalpha- positive, postmenopausal, early breast cancer patients., mutations may confer resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in lung adenocarcinoma patients with mutated EGFR, molecular or pharmacologic inhibition of the Lyn-PI3K/AKT pathway, markedly increased the sensitivity of the otherwise chemoresistant Cbl mutant-JMML cells to chemotherapeutic agents currently used in the treatment of JMML patients, PIK3CA mutation was found to be a frequent genetic change in all breast cancer subtypes but occurred with the highest rate in HR(+)/HER2(-) tumors, miR-1 may play an important role in the pathogenesis of NSCLC by regulating PIK3CA through the PI3K/Akt pathway., frequent PIK3CA amplification and promoter methylation of RASSF1A and PAX6 genes in gastric cancers, Studied the expression of phosphatidylinositol 3 kinase (PI3-K), protein kinase B (PKB) and glycogen synthase kinase 3 beta (GSK-3 beta) in skeletal muscle tissue of gestational diabetes mellitus patients., Studied the PIK3CA gene expression status and hotspot mutations in six cases of SDC by immunohistochemistry and genomic DNA sequencing., Data indicate that oncogenic activation of the phosphoinositide 3-kinase (PI3K) pathway involving phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) gene mutations can contribute to the progression of mucin-producing neoplasms, PIK3CA mutations frequently coexist with EGFR/KRAS mutations and may have a role in survival and prognosis, Data show the expression of N-myc downstream-regulated gene 2 (NDRG2) is frequently downregulated in adult T-cell leukaemia-lymphoma, resulting in enhanced phosphorylation of PTEN and activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway., These results reveal betaig-h3 enhances the metastasis potentials of human osteosarcoma cells via integrin alpha2beta1-mediated PI3K/AKT signal pathways., PIK3CA mutations are more common in HPV(+) OPSCC and are associated with activation of mTOR, but not AKT. These data suggest that inhibitors for mTOR may have activity against HPV(+) PIK3CA mutant oropharyngeal cancers., Data suggest that the expression of ATP-binding cassette sub-family G member 2 (ABCG2) and the side population may be regulated by phosphatase and tensin homologue deleted on chromosome -10 (PTEN) through the PI3K/Akt pathway., NGF regulates the expression of VEGF through the PI3K/mTOR signaling pathway in human HaCaT keratinocytes., Our data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence., Inhibition of PI3K (and mTOR) leads to an increase in catalase expression in MCF-7 breast cancer cells., PIK3CA mutations play a critical role in the genesis of rhabdomyosarcoma, PIK3CA gene was found to be mutated in 11 (22%) squamous cell anal carcinoma cases., The present experiments demonstrated a critical role for the GPRC6A-ERK1/2 and PI3K/Akt signaling pathway in arginine-mediated fibroblast survival., In this review, we discuss the emerging evidence for a functional relationship between the IGF-I/PI3K/AKT/mTOR pathway and ASDs, as well as a possible role of this signaling pathway in the diagnosis and treatment of ASDs. [review], Mutations in PIK3CA predict resistance to anti-EGFR therapies., Among the 42 patients who were seropositive for hepatitis B, 17 (40.5%) had HBx mutations and 4 (9.52%) had mutations in PIK3CA., Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin in colon cancer., the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status, is reported., We examined the response of 80 samples of primary cells from acute myeloid leukemia patients to selective inhibitors of the phosphatidylinositol 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis., Data indicate PI3K/Akt signaling as an essential pathway regulating the distribution of nucleolin., Consistent expression of the PI3K catalytic isoform PI3K p110alpha was detected in a panel of glioblastoma patient samples. Inhibition of PI3K p110alpha activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumor regression in vivo., Protein expression of PI3K, Akt and survivin were significantly associated with the development, progression and metastasis of gastric cancer and may have value as diagnostic and prognostic markers in gastric cancer., Aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD., Increased SOX2 gene copy number is associated with FGFR1 and PIK3CA gene gain in non-small cell lung cancer and predicts improved survival in early stage disease, PI3K-dependent binding of FOXO to the HBP1 promoter is part of a pathway that controls cell proliferation., PIK3CA isoform is of paramount importance for constitutive Akt activity in multiple myeloma , and - in contrast to inhibition of other class I isoforms - only the blockade of PIK3CA was sufficient to induce cell death in a sizeable subgroup of MM samples., TEIF is a downstream effector in EGF/PI3K/Akt signaling., Data demonstrate that the BRAF(V600E) cooperates with either PIK3CA(H1074R) or with silencing of the tumor-suppressor PTEN, to promote development of anaplastic thyroid carcinoma., This study indicated that mutations of KRAS, PIK3CA and NRAS were rare in advanced gastric cancer., We have identified no significant relationship between PIK3CA amplification, race (p= 0.630) and histological type (p=0. 731) in breast carcinoma, but correlation of PIK3CA amplification and age showed a significant relationship (p=0. 003) between them, These data indicate that HIV-1 might also promote PI3K signalling to balance processing of its transcripts by regulating phosphorylation of splicing regulatory proteins., E4-ORF1 interacts with Dlg1 and PI3K to assemble a ternary complex where E4-ORF1 hijacks the Dlg1 oncogenic function to relocate cytoplasmic PI3K to the membrane for constitutive activation., FAM3A plays crucial roles in the regulation of glucose and lipid metabolism in the liver, where it activates the PI3K-Akt signaling pathway by way of a Ca(2+) /CaM-dependent mechanism, Our results indicate that, besides HIF-1alpha, several other pathways, including PI3K/Akt, may be involved in the response to hypoxia of immature and, more specifically, of mature DC to sustain their trafficking and functions within hypoxic microenvironments., Dual MAPK and PI3K/Akt inhibition was detected., The expression of PIK3CA and survivin had a significant correlation with pathological grade and lymph node metastasis in the primary adenosquamous lung carcinoma patients., Chinese colorectal cancer patients with either KRAS or PIK3CA mutations are more susceptible to distant metastasis., We identified differential therapeutic vulnerabilities that emerge upon the loss of both PTEN and p53, and observed that combined inhibition of PARP and PI3K provides increased efficacy in hormone-insensitive advanced prostate cancer., MCP-1 was shown to have a role in activation of the ER1 by phosphorylating Ser167 via the PI3K/Akt/mTORC1 signaling pathway, Further experiments demonstrated that phosphatidylinositide 3-kinases/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) and extracellular regulated protein kinases (ERK)., Data indicate that upregulation of TRPM cation channel TRPM8 promoted epithelial-mesenchymal transition of breast cancer cells via activating c-akt protein/glycogen synthase kinase 3 beta (GSK-3beta) pathway., Data indicate that Src kinase participates in the regulation of apoptosis through Src/PI-3 K/Akt signaling pathway in Hep-2 cell line., PIK3CA single nucleotide polymorphism rs17849071 GT+GG genotype was inversely associated with P53 protein accumulation in breast cancer samples., PIK3CA mutations were observed in 11 of 79 cases (13.92%), including a rare mutation, Q546 P, that had not previously been reported in OSCC., Data indicate that combined PI3K inhibitor LY294002 and mitogen activated protein kinase kinase (MEK) inhibitor AZD6244 showed synergistic effect on inhibition of SKOV3/DDP cell growth by inducing apoptosis and blocking cell cycle., Findings implicate APOBEC3B activity as a key driver of PIK3CA mutagenesis and HPV-induced transformation., sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types, Shorter GT dinucleotide repeat in the intron 1 of PIK3CA gene is associated with increased risk of breast cancer in Iranian women., the transcriptional activity of nuclear beta-Catenin depends on PI3K activity and both factors synergize for full WNT signaling activity and are associated with distant metastasis in colon cancer, our results demonstrate that activation of the PI3K/Akt/mTOR/p70S6K signaling pathway is involved in S100A4-induced viability, migration, upregulation of VEGF and downregulation of E-cadherin in CRC cells., Results show that thioridazine regulates endothelial cell function and subsequent angiogenesis by inhibiting VEGFR-2/PI3K/mTOR signal transduction., Data indicate that malic enzyme 2 knockdown impacts phosphatidylinositol 3-kinases/proto-oncogene protein akt (PI3K/AKT) signaling., Results show that cell stimulation promotes p110alpha and p110beta association, demonstrating oligomerization of PI3K catalytic subunits within cells., Data indicate that combination of epidermal growth factor (EGFR) inhibitors with either the phosphatidylinositol 3-kinases inhibitor ZSTK474 or the mTOR serine-threonine kinases inhibitor sirolimus showed increased activity., Knockdown of AKT3 and/or PI3KCA genes in T98G cells led to a significant reduction in cell viability, the accumulation of subG1-phase cells and, a reduced fraction of cells in the S and G2/M phases., High expression of PI3K is associated with sinonasal and laryngeal small-cell neuroendocrine carcinoma., PIK3CA mutations are associated with classical markers of good prognosis and signatures of PI3K pathway activity. The presence of a PIK3CA mutation does not preclude a response to neoadjuvant anastrozole treatment., The combination of PI3K and CDK 4/6 inhibitors overcomes intrinsic and adaptive resistance leading to tumor regressions in PIK3CA mutant xenografts., Different targeted therapies may be necessary for Triple-negative breast cancer that involves activation of PIK3CA and AKT1 ., In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. These data demonstrate the feasibility and potential utility of mutation screening in the detection of a range of tumor biomarkers, PIK3CA mutations are associated with good response to docetaxel plus epirubicin neoadjuvant chemotherapy in breast cancer., We detected a mosaic disease-causing mutation in PIK3CA by sequencing of DNA extracted from cultured amniotic cells., Studies indicate the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway in breast cancer., PIK3CA mutations were not correlated with clinicopathological characteristics. However in the esophageal squamous cell carcinoma patients with family cancer history, PIK3CA mutations were independently correlated with worse overall survival., PTEN was neither a significant prognostic nor predictive factor. PIK3CA mutations were an adverse prognostic factor for survival but not predictive for lapatinib benefit., we have found that the PI3Ka/b isoforms and AKT are involved in the downstream mechanisms leading to actin polymerization, ATP secretion and aggregation of human platelets stimulated by 2-AG., KRAS, BRAF, and PIK3CA mutations were evaluated in 204 colorectal carcinoma samples; the frequency of KRAS, BRAF, and PIK3CA mutations was 23.5, 9.8, and 5.9 %, respectively., A significant percentage of Uterine malignant mesodermal mixed tumors, Uterine clear cell carcinomas, and Uterine serous carcinomas have mutations in PIK3CA., The presented data subclassified colorectal cancers (CRCs) based on their activated signaling pathways and identify a role for c-MET and IGF1R-driven PI3K signaling in CRCs, which is superior to KRAS mutational tests alone., The presence of PIK3CA and RAS mutations and other alterations affecting the mTOR pathway activity in HNSCC could be exploited to predict the potential resistance to cetuximab, PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors., PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer., Germline SNPs in the PI3 K-AKT-mTOR pathway were associated with breast cancer., It is anticipated that through an improved understanding of the biology of the PI3K/Akt pathway in prostate cancer, relevant biomarkers and rationale combination therapies will optimize targeting of this pathway, other mutation was in exon 19 of the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, resulting in a G-A substitution at position 1624 (E542K), The PI3K/AKT/mTOR pathway is distinguishable in SCLC genomic alterations. Therefore, a sequencing-based comprehensive analysis could stratify SCLC patients by potential therapeutic targets., Studies indicate that the PI3K/PTEN/Akt/mTOR pathway is in the pathogenesis of malignancies and development of resistance to anticancer therapies, and inhibitors are a promising therapeutic option., These results provide a rationale for targeting mutant RAS or PI3K/AKT/mTOR signaling in the subset of Erdheim Chester disease patients with NRAS or PIK3CA mutations., E2-induced Nrf2 activation was completely suppressed by the PI3K inhibitors., PIK3CA mutations were significantly related to ER/PR expression., Studies indicate that phosphatidylinositol 3-kinase (PI3K) pathway involved in glioblastoma (GBM) pathogenesis, and PI3K pathway inhibitors can help optimize GBM vaccine immunotherapy., PIK3CA mutations are associated with better outcomes in primary estrogen receptor positive disease and have been reported to be associated with resistance to human epidermal growth factor receptor 2 and endocrine therapies., Data show that IL-27 on IFN-gamma mediated autophagy perpetuates by simultaneous induction of kinases mTOR via JAK/PI3 K/Akt cascade and increment in myeloid cell leukemia sequence 1 (Mcl-1) level through PI3 K pathway., Data indicarte that Helicobacter pylori infection promotes protein synthesis through phosphatidylinositol 3 kinase/mTOR serine-threonine kinases(PI3K/Mtor)., KRAS (41%) and PIK3CA (8%) mutations in Colorectal cancer in patient-derived xenograft models closely paralleled patient tumors (35 to 51% KRAS, 12 to 21% PIK3CA)., HER2-positive breast carcinomas with a PIK3CA mutation are less likely to achieve a pCR after neoadjuvant anthracycline-taxane-based chemotherapy plus anti-HER2 treatment, even if a dual anti-HER2 treatment is given., In this review we present a state of art review on various classes of small molecule inhibitors selectively involving PI3K/Akt/mTOR pathway and their clinical potential in this disease., Mutations in the TP53 gene and to lesser extent in the PIK3CA gene seem more frequent in cervical adenocarcinoma than in squamous cell carcinoma and CIN3, Aberrant activation of PI3K pathway leads to increased phosphorylation of a surprisingly wide variety of kinases and downstream signalling networks., Impaired EPCs proliferation could be reversed by BBR via the PI3K/AKT/eNOS signaling pathway., RI represents an important predictor of progression in patients with CRC and suppresses proliferation and metastasis in CRC cells through inhibiting PI3K/AkT pathway., High PI3K is associated with hepatocellular carcinoma., The phosphoinositide 3-kinase/Akt signaling pathway was activated in cells overexpressing Sox2., Data indicate that quercetin induces apoptosis via phosphatidylinositol 3-kinase PI3k/Akt pathways, suggesting quercetin has potential to be used as an anti-tumor agent against human cervix cancer., These results suggest that the combination of a selective MEK inhibitor and a PI3K/mTOR inhibitor was effective in CRC harboring with KRAS and PIK3CA mutations., Report PIK3CA mutation status in colorectal neoplasms and neuroendocrine differentiation in primary/metastatic colorectal neoplasms., Studied the structure and dynamics of the PIK3CA wild-type and H1047R oncogenic mutant., HER3 knock down decreases cell proliferation preferentially in PIK3CA kinase domain mutation (H1047R) cells., Classification by PIK3CA and SOX2 protein expression is useful for predicting the prognosis of Asian patients with lung SQCC with stage I., Studies indicate that phosphatidylinositol 3-kinases (PI3Ks) and phosphatidylinositol 3-kinase-related protein kinases (PIKKs) are two related families of kinases and share very similar kinase domains., PIK3CA hotspot mutations are present at a relatively high frequency in CTCs and their presence is associated with worse survival in patients with breast cancer with metastasis., PIK3CA gene mutation is a good indication of breast cancer development in early diagnosis of cancer., MALAT1 might suppress the tumor growth and metastasis via PI3K/AKT signaling pathway., Breast cancers harboring oncogenic PIK3CA activate SGK3 signaling while suppressing Akt, indicative of oncogenic functions for both INPP4B and SGK3 in these tumors., certain Akt/mTOR/4E-BP1 pathway signals could be novel therapeutic targets for Merkel cell carcinomas regardless of Merkel cell polyomavirus infection status, Patients with HER2-amplified tumors were more likely to present PIK3CA mutations compared to patients with triple negative tumors., Data show that the combination of PI3 kinase inhibitors with ErbB receptors HER2/HER3 targeting antibodies may constitute a promising therapeutic strategy for prostate cancer., Data indicate that phosphatidylinositol-45-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations have no negative impact on survival after surgery or systemic therapy. However, Tim-3 triggers growth factor type responses in acute myeloid leukaemia cells by activating a phosphatidylinositol-3 kinase (PI-3K)/mammalian target of rapamycin (mTOR) pathway., Combination therapy of PI3Kis with IGF1R inhibitors for treating IGF1R-positive human cancers., Study sequenced a large clinical series of patients with metastatic colorectal cancer (mCRC) for RAS and PIK3CA mutations. RAS alterations occurred in 48% of mCRC cases, with mutations within KRAS exon 2 in 43%, KRAS exons 3 and 4 in 3%, and NRAS in 2% of cases. PIK3CA mutations occurred in about 10% of mCRC and were significantly associated with concurrent RAS mutation., While P7170 inhibits PI3K and mTOR in ER+/HER2- human breast cancer cells and tumors ex vivo, in vivo data indicate that the primary mechanism of P7170 anti-tumor action is inhibition of mTOR and cell proliferation, Data indicate that pretreatment of BEZ235 can confer the radiation-inducing phosphoinositide 3-kinase/mammalian target of rapamycin/AKT signaling pathway, and further inhibit the cell viability., Data indicate that ibrutinib significantly reduced PI3K-Akt activity in cardiac cells., AKT3, PI3KCA, and VEGFR2 silencing reduces the invasiveness of glioblastoma multiforme T98G cells., Drugs interfering with expression and activity of XIAP re-sensitize mutant PIK3CA colorectal cancer cells to TRAIL-induced cell death., self-renewal versus differentiation of human ESCs (hESCs) in response to Wnt signaling is predominantly determined by a two-layer regulatory circuit involving beta-catenin, E-cadherin, PI3K/Akt, and Slug in a time-dependent manner., The purpose of the study was to investigate the heterogeneity of PIK3CA mutational status within single circulating Tumor Cells isolated from individual metastatic breast cancer patients., Combined analysis of PIK3CA mutation and PTEN expression may serve as critical indicators to identify patients unlikely to respond to trastuzumab., The expression of both PIK3CA and PIK3CB is increased and related to the development and progress of colorectal carcinoma and multidrug resistance, we will summarize the current knowledge about the role of PAM ( PI3K/AKT/mTOR) signaling in medulloblastoma and discuss the strategies that are currently being evaluated with targeted agents against this pathway., High tumor PI3K signaling was correlated with adverse survival outcome in patients with rectal cancer., suggests that PIK3CA mutations account for a small fraction of PI3K pathway activation and have a limited impact in interfering with the BRAF/NRAS-driven growth in melanoma, our results unveil a functional cross-talk between YB-1, DeltaNp63alpha and the PI3K/AKT pathway critically governing survival of squamous carcinoma cells., PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer, The present study emphasizes that the treatment for breast cancer should include molecular analysis of relevant driver mutations with priority to PIK3CA gene while taking clinical decisions in breast cancer patients., Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature., PIK3CA amplifications and mutations in Non-small cell lung cancer have been reported in 37% and 9%, respectively. Both are poor prognostic factors in Squamous Cell Carcinoma., PIK3CA, SMAD4, and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases., Lastly, 17.5% of hepatocellular carcinoma paradoxically had diffuse loss of the oncoprotein p110alpha compared with strong expression in background cirrhotic liver, The PIK3CA hotspot mutations E542K, E545K, and H1047R were found to be significantly more prevalent in PIK3CA-mutant MSS (21/58, 36%) compared to PIK3CA-mutant MSI-H EECs (5/37, 13.5%; p=0.019)., Data show that licochalcone A (LicoA) suppresses solar UV-induced cyclooxygenase (COX-2) expression by acting as a potent inhibitor of enzymes PI3K, MEK1, and B-Raf., findings identify PI3K/AKT pathway mutations as an important cause of epileptogenic brain malformations and establish megalencephaly, hemimegalencephaly, and focal cortical dysplasia as part of a single pathogenic spectrum., Mutations in the PI3K pathway seem therefore to be an important parameter to predict absence of response to cetuximab., Circulating tumor DNA containing PIK3CA mutations is highly predictive of shorter recurrence-free survival and overall survival in primary breast cancer patients., Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS., Overexpression of STAT1 or of a constitutively active PI3Kalpha mutant failed to induce basal IDO production, PI3K is activated after imatinib secondary resistance in gastrointestinal stromal tumors., PIK3CA and AKT2 mutations occurred at low frequency in gastric cancer., Somatic mutations and copy number amplification of PIK3CA were associated with response to CCRT in patients with cervical squamous cell carcinoma., The frequency of mutations in either KRAS or PIK3CA were significantly higher in patients without lymph node metastasis than those with., PIK3CA mutation is associated with breast cancer., Study demonstrates the oncogenic cooperation between PI3K and Yap pathways along liver carcinogenesis. The PIK3CA/Yap mouse represents an important preclinical liver tumor model., These findings provide evidence that a miR-520a binding site polymorphism rs141178472 in the PIK3CA 3'-UTR may play a role in the etiology of colorectal cancer, This result suggests polymorphic GT repeat of PIK3CA gene may be a potential predictive marker of colorectal cancer risk in Iranian population, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature esophageal squamous cell carcinoma., PIK3CA mutations often affect a limited fraction of transformed metastatic colorectal cancer cells., Data indicate that high-grade serous ovarian carcinoma (HGSC) cell lines with high GRB2 associated binding protein 2 (GAB2) expression are more responsive to phosphatidylinositol 3-kinases (PI3K) inhibitor PF-04691502., The PIK3CA mutations within our engineered cell model did not lead to enhanced oncogene-dependent cell death when treated with direct inhibition of the PI3K enzyme yet did show increased sensitivity compared with control with dual PI3K/mTOR inhibition., Despite the rare prevalence of the 5 most common PIK3CA mutations in Langerhans cell histiocytosis, this report highlights that the PI3K-AKT pathway could be implied in the pathogenesis of Langerhans cell histiocytosis., Among 264 patients, mutations in KRAS exon 2, KRAS exons 3 or 4, NRAS, BRAF and PIK3CA were detected in 34.1%, 3.8%, 4.2%, 5.4% and 6.4%, respectively. Thus, a total of 12.1% of patients without KRAS exon 2 mutations had other RAS mutations, MiR-10b directly targets the 3'-UTRs of ZEB1 and PIK3CA., Data show that microRNA miR-21 plays an oncogenic role in diffuse large B-cell lymphoma (DLBCL) by modulating the PI3-Kinase/AKT protein/mTOR protein/forkhead box O1 protein (FOXO1) pathway at multiple levels resulting in strong prognostic implication., Data show that microRNA miR-451 target tuberous sclerosis 1 (TSC1) gene and activates the PI3-kinase/Akt protein/mTOR protein signaling in multiple myeloma (MM) Side population (SP) cells., Proteins induced by PIK3CA mutations correlated with EGFR signaling and reduced relapse-free survival in basal-like breast cancer., PI3KCA gene polymorphism is associated with poor drug response in metastatic renal cell carcinoma., treatment with butein significantly increased reactive oxygen species (ROS) generation and reduced the phosphorylation of PI3K, AKT and mTOR expression, which contributes to the inhibition of the tumor growth of cervical cancer, The prevalence of PIK3CA mutation status in colorectal cancer does not differ according to race/ethnicity, but may vary according to other relevant clinicopathologic and etiologic factors, PIK3CA amplification may be an early and important event in colorectal carcinogenesis and may drive the development of left-side tubular adenomas independently with KRAS mutation., our results demonstrate that miR-375 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in osteosarcoma., Data show that PI3 kinase is an attractive therapeutic target in malignancies induced by proto-oncogene protein c-Kit mutations., The aim of the present study was to obtain the first data for the phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) mutation frequency among nonsmall-cell lung cancer (NSCLC) patients in Turkey., This is the first study identifying the PIK3CA mutation specifically in sporadic cribriform-morular variant of papillary thyroid carcinoma, we also explored the downstream molecules of miR-19a/PIK3CA signaling. We found that Notch signaling was induced by upregulation of miR-19a, and inactivation of Notch signaling attenuated the cell proliferation, migration and invasion promoted by miR-19a, Loss of PIPKIgamma or its focal adhesion-targeting variant, PIPKIgammai2, impaired PI3K/Akt activation upon stimulation with growth factors or extracellular matrix proteins in different tumor cells., PIK3CA Mutation and Amplification is not associated with Clinicopathological Characteristics of Gastric Cancer., ata show that activation of EphB2 receptor kinase arrests tau protein hyperphosphorylation through phosphatidylinositol 3-kinase (PI3K)/Akt protein-mediated glycogen synthase kinase-3beta (GSK-3beta) inhibition., Analysis of interdomain interactions of wild-type and mutants at the p110alpha-p85alpha interface with molecular dynamics simulations suggest that tumor-associated mutations weaken interactions between p110alpha and p85alpha by disrupting key stabilizing interactions., It also inhibited extrinsic pathway protein caspase 8, growth-related protein PI3K and further activated PTEN in combination with cisplatin., Mutations of PIK3CA occur in approximately 20% of urothelial carcinoma ,and often include gain-of-function mutations that involve the helical and kinase domain., Genomic amplifications through copy gain of the PI3KCA have been frequently found in Follicular thyroid carcinoma (in 24% of tumors) and Anaplastic thyroid carcinoma (in 42% of tumors)., Data show that immunoglobulin-like transcript 4 (ILT4) increases the expression of the co-inhibitory molecule B7-H3 through PI3K/AKT/mTOR signalling., HSP60 overexpression increases the protein levels of the p110alpha subunit of phosphoinositide 3-kinase and c-Myc, Case Report, Studied how rapamycin affects CCN2 expression and migration of lung fibroblasts in vitro; PI3K and inhibitors were used to determine rapamycin's mechanism of action., the current study illustrated that downregulation of miR203 and overexpression of PIK3CA were novel potential prognosis predictors of gastric cancer patients, Found no association between PIK3CA mutational status and other clinical/biological parameters in breast cancer treated with adjuvant trastuzumab., there is a key effect of PIK3CA(H1047R) on mammary cell fate in the pre-neoplastic mammary gland and the cell of origin of PIK3CA(H1047R) tumours dictates their malignancy, thus revealing a mechanism underlying tumour heterogeneity and aggressiveness, oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumour initiation, setting the stage for future intratumoural heterogeneity, Studied the global phosphotyrosine proteome of isogenic knock-in cell lines containing two hotspot mutations in PIK3CA (E545K and H1047R); 824 unique phosphopeptides were identified., Findings indicate inositol polyphosphate 5-phosphatase PIPP (INPP5J) as a suppressor of oncogenic phosphoinositide 3-kinase (PI3K)/AKT signaling in breast cancer., Distinct beta-catenin and PIK3CA mutation are linked in endometriosis-associated ovarian endometrioid and clear cell carcinomas, It plays a role in cell survival, cell differentiation and cell proliferation in neoplasms., Data show that leukemia inhibitory factor (LIF) signaling promote chemoresistance in cholangiocarcinoma by up-regulating myeloid cell factor-1 (Mcl-1) via phosphatidylinositol 3-kinase (PI3K)/c-akt protein (AKT)-dependent pathway., assessed the clinical impact of changes in the frequency and topology of PIK3CA mutation and HER2 (ERBB2) amplification within HER2-positive breast cancer during neoadjuvant the, Results show that oncogenic PIK3CA mutations in HER2/neu overexpressing uterine serous carcinoma cells are common and may constitute a major mechanism of resistance to trastuzumab., Data show that dual epidermal growth factor receptor 2 HER2/phosphatidylinositol 3-kinase PIK3CA blockade may be a drug therapy for uterine serous carcinoma (USC) with HER2 gene amplification and mutated wild-type PIK3CA resistant to chemotherapy., analysis of ARID1A, CDH1, cMET and PIK3CA expression and target-related microRNA expression in gastric cancer, Case Report, Somatic mutations in PIK3CA have roles in PIK3CA-related somatic overgrowth spectrum, We describe the case of a patient in whom we were able to confirm a causative PIK3CA mutation., the presence of PIK3CA major mutations of cell-free DNA could be a discriminatory predictor of survival in early-stage triple negative breast cancer, Data show that rapamycin-insensitive companion of mTOR protein (RICTOR) plays a central role in phosphatidylinositol 3-kinase (PI3K)/proto-oncogene protein c-akt (AKT) pathway in melanocytes and its deregulation could be involved in melanoma development., patients with mutant PIK3CA had distinct characteristics in age, menopausal status, and histological subtype and have better treatment outcome and less distant metastasis after surgery-based multimodal therapy., Overexpression of PI3K-p110alpha is associated with progression of uterine cervical neoplasia, and the expression of pAkt and DJ-1 is positively correlated with PI3K-p110alpha expression in this process., Down-regulation of PIK3 is associated with osteoporosis., 29b lowers postoperative IOP and sustains the function of filtering bleb. It inhibits the proliferation of fibroblasts and reduces collagen deposition by repressing the PI3K/Akt/Sp1 pathway in rabbits subjected to GFS., no prognostic significance of specific PIK3CA mutations in breast cancer treated with adjuvant chemotherapy, We have observed a 4% oncogenic mutation frequency of the PIK3CA gene, which plays a minor role in the development of OSCC in an Indian population., Data show that RNA silencing of CCN family member 1 protein (CCN1) inhibits umbilical vein endothelial cell (HUVEC) proliferation under hypoxic conditions by inhibiting phosphoinositide 3-kinase (PI3K)/AKT protein signaling., Data show that low-level phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) mutations were detectable in the serum indicating the utility of cell free DNA (cfDNA) as a DNA source to detect mutations in metastatic biliary cancers., Data show that puquitinib mesylate (XC-302) induced autophagy in nasopharyngeal cancer cells CNE-2 by promoting cell autophagy and inhibits the phosphatidylinositol 3-Kinase (PI3K)/AKT protein/TOR serine-threonine kinases (mTOR) signaling pathway., Data suggest that the overexpression of microRNA miR16 inhibits the proliferation, invasion and metastasis of hepatocellular carcinoma cells associated with the, PIK3CA mutation is associated with response to therapy in Breast Cancer., Data show that the combination of a phosphatidylinositol 3-Kinase (PI3K)/mTOR protein inhibitor with an androgen receptor {AR) inhibitor results in a synergistic anti-tumor response in non-castration-resistant prostate cancer (CRPC) and CRPC models., Data indicate the role of tropomyosin-related kinase-B (TrkB) in activation of the interleukin-6/Janus kinase 2/STAT3 transcription factor and PI3 kinase/c-AKT proto-oncogene protein pathway in breast cancer., PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC., High PI3K p110alpha expression contributes to MET inhibitor resistance in gastric carcinoma xenografts., PIK3CA mutations were observed in 32% (8) of the 25 breast cancer tissues examined, Sequencing of exon 2 of KRAS suggested that 20% (5) of the 25 samples harbored a mutation and 16% (4) of BRAF harbored a mutation., miR-203 represses NF-kappaB signaling via targeting TAK1 and PI3KCA and miR-203 overexpression may contribute to the COPD initiation., Somatic activating PIK3CA mutations cause venous malformation., As depicted in Figure 3, APC (25%) followed by KRAS (20%), TP53 (14%), and PIK3CA (11%) were the most frequently mutated genes., Findings of frequent mutations in CDKN2A, NOTCH1, PIK3CA, and EGFR (all in excess of 20%) point to potential therapeutic avenues. Trials of targeted therapies directed toward these mutations should be explored., Study shows that high EGFR protein expression and exon 9 PIK3CA activating mutations are independent prognostic factors in triple negative breast cancers., Data show that 14-3-3beta protein augmented the expression of matrix metalloproteinasea MMP2 and MMP9 through PI3 kinase/Akt protein/NF-kappaappa B pathway, thereby enhancing the invasiveness of hepatocellular carcinoma (HCC) cells., effects. Further studies indicated that PRKCI knockdown-mediated autophagy was associated with the inactivation of phosphatidylinositol 3-kinase alpha/AKT-mammalian target of rapamycin (PIK3CA/AKT-MTOR) signaling., Therefore, we identified a tumorigenic role of Id-1 in OS and suggested a potential therapeutic target for OS patients., Based on the collective findings, we suggest that vIRF2 acts as an activator in PI3K/Akt pathway., KRAS and PIK3CA mutations can influence the response of DLD1 colorectal cancer cell lines to MEK and PI3K inhibitors, but that the effect is dependent on the experimental model used to assess drug sensitivity., Though Wortmannin was found to nullify the effect of H1047R over the PIK3CA, further studies are required for designing a better compound., No relation was found between PIK3CA expression and clinical features of ovarian clear cell carcinoma. PIK3CA expression had no impact on survival., PIK3CA mutations detected at high frequencies in breast cancer and mostly associated with better or insignificant outcomes in estrogen receptor-positive (ER+) early stage breast cancer and tend to be with worse prognosis in ER- disease., Low incidence of PIK3CA mutations in adenocarcinomas of the ampulla of Vater suggest no major role in tumorigenesis., Our study demonstrates that the IGF1R/p110b/AKT/mTOR axis confers resistance to BYL719 in PIK3CA mutant breast cancers, The FGFR3, PIK3CA, TERT mutations, along with aberrant DNA methylation patterns, can serve as reliable genetic markers for the diagnosis of urinary bladder cancer. (Review),
OMIM_DISEASE Breast cancer, somatic, Colorectal cancer, somatic, Hepatocellular carcinoma, somatic, Nevus, epidermal, somatic, Ovarian cancer, somatic, Keratosis, seborrheic, somatic, Nonsmall cell lung cancer, somatic, Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, CLOVE syndrome, somatic, Gastric cancer, somatic, Cowden syndrome 5,
SP_COMMENT catalytic activity:ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate., disease:Defects in PIK3CA are associated with breast cancer [MIM:114480]., disease:Defects in PIK3CA are associated with colorectal cancer (CRC) [MIM:114500]., disease:Defects in PIK3CA are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome., disease:Defects in PIK3CA may underlie hepatocellular carcinoma (HCC) [MIM:114550]., disease:PI3KCA mutations affecting exons 9 and 20 display gender-and tissue-specific patterns, thus suggesting that the different amino acid changes could exert distinct functional effects on the oncogenic properties of this enzyme. Furthermore, sexual dimorphisms and tissue specific factors might directly or indirectly influence the occurrence of PI3KCA cancer alleles., function:Phosphorylates PtdIns, PtdIns4P and PtdIns(4,5)P2 with a preference for PtdIns(4,5)P2., similarity:Belongs to the PI3/PI4-kinase family., similarity:Contains 1 C2 domain., similarity:Contains 1 PI3K/PI4K domain., subunit:Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunit. Binds to IRS1 in nuclear extracts. Interacts with RUFY3.,
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta(PIK3CB) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta(PIK3CB) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3q22.3,
ENSEMBL_GENE_ID ENSG00000051382,
GENERIF_SUMMARY These results indicate that in addition to their roles in recruiting the catalytic subunit of PI3K to the insulin receptor substrate proteins, both p85alpha and p85beta play negative roles in insulin signaling, A function for phosphoinositide 3-kinase beta lipid products in coupling beta gamma to Ras activation in response to lysophosphatidic acid., It is unlikely that the promoter polymorphisms -359T/C and -303A/G of the catalytic subunit p110beta gene of human PI 3-kinase have a major impact on insulin secretion, insulin sensitivity, or the risk of type 2 diabetes, p110 has a role in activation of PI3K gamma along with G beta gamma, determinination of the involvement of PI3K and MAPK pathways and the importance of cross-talk between these pathways, in glucose-potentiated vascular smooth muscle cell chemotaxis to serum factors, Data highlight the differential signaling by p110alpha and -beta isoforms., Introduction of a pH1 vector producing shRNA (short hairpin RNA) that targets p110beta abolished PIA [N6-(2-phenylisopropyl)adenosine]-induced Akt activation, although introduction of activating mutations from p110alpha at the corresponding sites in p110beta failed to render the enzyme oncogenic in human cells, the possibility remains that other mutations might activate the beta isoform, p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase have roles in oncogenic transformation, Reduced activation of NF-kappaB via impaired PI3K/Akt activation under increased TNF-alpha levels could result in increased apoptosis of vitiliginous keratinocytes., bFGF augments hypoxia induced VEGF release in breast cancer cells mainly through the PI3K pathway and partly depending on HIF-1 activity., C allele is a causal variant capable of attenuating insulin resistance in obese children., Our data indicate that different signalling pathways are involved in retinoic acid-induced up-regulation of the secretases., PI3Kalpha and -beta present distinct activation requirements and kinetics in G(1) phase, with a selective action of PI3Kalpha at the G(0)/G(1) phase transition, Phosphoinositide 3-kinase p110beta inhibitor TGX-221 inhibited shear-induced platelet activation and protected platelet function during extracorporeal circulation., p85alpha and p110beta are essential for androgen-stimulated AR transactivation, and their aberrant expression or activation might play an important role in prostate cancer progression, required for sphingosine-1-phosphate -induced endothelial cell migration through activation of Rac1, Although p110alpha activation is required to sustain the proliferation of established PIK3CA-mutant tumors, PTEN-deficient tumors are dependent instead on p110beta signaling., Rs361072 promoter variant of PIK3CB is associated with insulin resistance not with type 2 diabetes., PI3K p110beta positively controls lipopolysaccharide-induced interleukin-12 production through the c-jun kinase (JNK)-1-dependent pathway in human macrophages and dendritic cells., PI3Kbeta plays an essential role in GPVI-mediated platelet aggregation and Akt activation, phosphoinositide 3-kinase isoforms alpha and beta have roles in glycoprotein VI-induced platelet signaling and thrombus formation, Our results support the concept that p110beta appears to be the predominant functional class I PI 3-kinase isoform in prostate cancer cells., Data show that similar responses were seen in cancer cells with wild-type or activated mutant PI3K genes treated with p110alpha/delta or p110alpha/beta/delta inhibitors in cell viability assays., minor G allele of PIK3CB associates with decreased muscle subunit ratio and lower hepatic glucose production at high plasma insulin levels., This study shows that the enhanced transforming potential of p110beta is the result of its decreased inhibition by p85, due to the disruption of an inhibitory C2-iSH2 domain interface., In hyperglycemic leptin-deficient Lep(ob/ob) transgenic mice, leptin acutely and potently improves glucose metabolism, before any change of body fat mass, via a mechanism involving the p110alpha and -beta isoforms of phosphatidylinositol-3-kinase., Significance of this altered regulation in tumor models of PTEN deletion, as well as the potential implications of the unique p110beta regulation on GPCR-driven tumorigenesis., lipid kinase p110beta/p85beta elucidates an unusual SH2-domain-mediated inhibitory mechanism, study shows that p110beta nuclear localization signal and p85beta nuclear export sequence regulate p85beta/p110beta nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110beta controls cell survival, Results define PI3Kbeta as a potential therapeutic target in inflammatory disease., This paper reports the first purification of a phosphoinositide 3-kinase and shows that the protein is a heterodimer of an 85 kd regulatory subunit that mediates binding to phosphorylated proteins and a 110 kd catalytic subunit., results suggested that down-regulation of p110beta expression by siRNA obviously reduced cell number via accumulation in G(0)-G(1) phase of the cell cycle., Combined blockade of P2Y12, P2Y1 and PI3-kinase p110beta fully prevents platelet and leukocyte activation during hypothermic extracorporeal circulation., Phosphoinositide 3-kinase C2beta regulates RhoA and the actin cytoskeleton through an interaction with Dbl, p110beta was activated near metaphase and controlled dynein/dynactin and Aurora B activities in kinetochores, chromosome segregation, and optimal function of the spindle checkpoint, Disrupting the p110beta-Gbetagamma interaction by mutation or with a cell-permeable peptide inhibitor blocked the transforming capacity of PI3Kbeta in fibroblasts and reduced the proliferation, chemotaxis, and invasiveness, Data indicate that phosphatidylinositol 3'-kinase (PI3K) alpha and beta p110 isoforms of PI3K are broadly expressed in myeloma., In mammalian cells, p110beta acts as a molecular sensor for growth factor availability and induces autophagy by activating a Rab5-mediated signaling cascade., p110alpha acts as a negative regulator of beta cell exocytosis and insulin secretion, while p110beta is a positive regulator of insulin secretion through a mechanism separate from its catalytic activity, Data sugget that the E633K mutant activates p110beta by enhancing its basal association with membranes., genetic association study in a population in Sweden, HSP20 directly associates with PI3K subunits and suppresses its activity in hepatocellular carcinoma, resulting in the inhibition of the AKT pathway, and subsequently decreasing the growth of hepatocellular carcinoma., PI3Kbeta expression was elevated significantly in lung squamous cell carcinomas (SCC) compared with adenocarcinomas, Results show that cell stimulation promotes p110alpha and p110beta association, demonstrating oligomerization of PI3K catalytic subunits within cells., The score was higher in metastatic compared to primary lesions (P<0.001) and was significantly associated with potential measures of PI3K activation, Phosphoinositide 3-kinase beta mediates microvascular endothelial repair of thrombotic microangiopathy., PI3Kbeta regulates the nuclear envelope through upstream regulation of RCC1 and Ran, Platelet PI3Kbeta and GSK3 regulate thrombus stability at a high shear rate., PIK3CB is critically involved in response to preoperative radiotherapy and may serve as a novel target for therapeutic intervention., The expression of both PIK3CA and PIK3CB is increased and related to the development and progress of colorectal carcinoma and multidrug resistance, Overexpression of P110BETA accelerated differentiation in C2C12 cells and primary human myoblasts through an Akt-dependent mechanism, while expression of kinase-inactive P110BETA had the opposite effect., Our findings provide new insight into the genetic mechanisms underlying PI3K pathway activation in human tumors and indicate that PIK3Cb(D1067V) is a rational therapeutic target in certain cancers., TNFR1 Regulates Ovarian Cancer Cell Tumorigenicity Through PIK3CB-p110Beta, Collectively, these results highlight the cleavage of shp-1 as a critical event in reprogramming LPS pathway to promote both neutrophil recruitment and survival and provide a novel mechanistic framework for the investigation of the post-traumatic MODS., expression levels distinguish chronic lymphocytic leukemia B cells from normal B lymphocytes, miR-130a plays a critical role in attenuation of cardiac dysfunction and remodeling after myocardial infarction. The mechanisms involve activation of PI3K/Akt signaling via suppression of PTEN expression., our findings provide for the first time that PF-04691502 inhibits the constitutively activated PI3K/mTOR pathway in aggressive B-cell NHL cell lines associated with inhibition of cell cycle progression, cell proliferation and promotion of apoptosis., The results of this study demomstrated that PI3 kinase mutations as novel prognostic markers in gliomas., PIK3CB D1067Y mutant behaved as an oncogene and transformed normal cells, an activity that was enhanced by PTEN depletion., Our study demonstrates that CSE/H2S system is regulated by miR-216a, and regulates ABCA1-mediated cholesterol efflux and cholesterol levels through the PI3K/AKT pathway., The data provide the first evidence that SJP protects SH-SY5Y cells against 6-OHDA toxicity possibly by inhibiting MAPK and NF-kappaB and activating PI3K/Akt signaling pathways., Our results demonstrated the pro-inflammatory and angiogenic effects of PlGF on HIMECs in IBD through activation of PI3K/Akt signaling pathway. PlGF/PI3K/Akt signaling may serve as a potential therapeutic target for IBD., Mefloquine acts on gastric cancer cells via suppressing PI3K/Akt/mTOR pathway., Our data suggested a potential role of Rab11-FIP2 in tumor progression and provided novel insights into the mechanism of how Rab11-FIP2 positively regulated cell migration and invasion in CRC cells., Our study demonstrates that the IGF1R/p110b/AKT/mTOR axis confers resistance to BYL719 in PIK3CA mutant breast cancers.,
SP_COMMENT catalytic activity:ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate., function:Phosphorylates PtdIns, PtdIns4P and PtdIns(4,5)P2 with a preference for PtdIns(4,5)P2., pathway:Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis., similarity:Belongs to the PI3/PI4-kinase family., similarity:Contains 1 PI3K/PI4K domain., subunit:Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunit., tissue specificity:Expressed ubiquitously.,
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(PIK3CD) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(PIK3CD) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1p36.2,
ENSEMBL_GENE_ID ENSG00000171608,
GENERIF_SUMMARY PI3K delta can play a selective role in the amplification of phosphatidylinositol (3,4,5) trisphosphate (PIP3) levels that lead to neutrophil polarization and regulate directional migration, but not random locomotion., p110delta isoform of PI3K is consistently expressed at a high level in blast cells from AML, in contrast to the other class I isoforms, Stimulation of TNF-alpha-primed human neutrophils with fMLP results in biphasic activation of PI3K; the first phase is largely dependent on PI3Kgamma; the second phase is largely dependent on PI3Kdelta and regulates parallel activation of ROS production, p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase have roles in oncogenic transformation, These findings could shed light on further understanding the polymorphisms of p110delta in B-cell immunodeficiency and different populations., p110delta contributes significantly to Th cell expansion and differentiation in vitro and in vivo, also in the context of CD28 costimulation., This review describes the second-messenger PI3K delta signalling pathways that are involved in immune responses relevant to the pathogenesis of rheumatoid arthritis and other inflammatory diseases., identifies the RhoA/ROCK pathway as a major target of p110delta-mediated PI3K signalling, novel function of the class I(A) PI3K isoform p110delta in neuroblastoma growth and survival., These results demonstrate that CD148 may interact with and dephosphorylate p85 when it is phosphorylated and modulate the magnitude of phosphoinositide 3-kinase activity., In contrast with PI3Kalpha, beta and gamma, PI3Kdelta accounts for most of the PI3K-dependent signaling ruling the production of IL-1beta, IL-6, TNF and sIL-1Ra in monocytes., Results identify a conserved phosphoinositide 3-kinase p11delta promoter region that may account for the predominant leukocyte expression of p110delta., RUNX1 may play a critical role in chemotherapy response in acute megakaryocytic leukemia by regulating the PI3-kinase/Akt pathway., These studies establish that previously activated memory T cells are at least as sensitive to p110delta inhibition as naive T cells and show that mouse models accurately predict p110delta function in human T cells., Data show that similar responses were seen in cancer cells with wild-type or activated mutant PI3K genes treated with p110alpha/delta or p110alpha/beta/delta inhibitors in cell viability assays., PI3Kdelta expression and signaling is increased in the lungs of patients with COPD., IFN-beta triggers an atypical MEK2/PI3Kdelta signaling cascade to regulate sIL-1Ra expression in monocytes., These observations suggest that PI3Kdelta contributes to induction of enhanced systemic lupus erythematosus memory T cell survival, PI3K p110delta is important for TGFB1 induced production of the contractile proteins calponin and alpha-SMA and the proinflammatory cytokine IL-6, p37delta appears to be a new tumor-specific isoform of p110delta with growth-promoting properties, Isoform specific targeting of PI3Kdelta may be beneficial in the treatment of glioblastoma multiforme by specifically inhibiting tumour cell migration capacity., p110delta-dependent translocation of exogenous CSF-1 to the nucleus-associated CSF-1Rs, correlating with a prominent role of p110delta in activation of the Rab5 GTPase, a key regulator of endocytic trafficking, Findings suggest that excessive PI3Kdelta activity is characteristic in Hodgkin lymphoma (HL) and support clinical evaluation of GS-1101, alone and in combination, as targeted therapy for HL., present a detailed biochemical and bioinformatic characterization of p110delta gene regulation, demonstrating that PIK3CD has distinct promoters, some of which can be dynamically activated by pro-inflammatory mediators, PI3 kinase delta is a key regulator of synoviocyte function in rheumatoid arthritis., PIK3CD shows evidence of association with schizophrenia, and is a previously undescribed therapeutic target for the treatment of psychiatric disorders., Studies indicate that the research with phosphoinositide 3-kinase p110-delta (p110delta) in chronic lymphocytic leukemia (CLL) have led to a more fundamental understanding of CLL signaling defects., High PIK3CA/PIK3CD ratio identified a subset of primary mantle cell lymphomas resistant to GS-1101 and this ratio increased significantly with relapse., The expression of PIK3CD is inversely correlated with miR-30a levels in metastatic colorectal carcinoma tissues., These results suggest that PI3Kdelta mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-kappaB., this study found E1021K in 17 patients with activated PI3K-delta syndrome (APDS), from seven unrelated families with, but not among 3346 healthy subjects., Data indicate that patients with combined immunodeficiency disease who share gain-of-function mutations in PIK3CD (p110delta), resulting in hyperactivation of mTOR signaling and skewed the differentiation of CD8+ T cells., Study reveals functional and mechanistic links between miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of colorectal carcinoma., PI3Kdelta contributes to multiple aspects of the pathogenic FLS behavior in RA. These observations, together with previous findings that PI3Kdelta regulates FLS growth and survival, PIK3CD is a target gene of miR-125b in Ewing's sarcoma cells. RT-PCR and western blot assays identify over-expression of miR-125b that suppresses the expression of PIK3CD mRNA and protein., PIK3CD was inversely correlated with miR-663 in glioblastoma specimens and predicted poor prognosis of patients with glioblastoma, Gestational diabetes mellitus is accompanied by leukocyte PIK3CD overexpression associated with reduced plasma LDL-C and TC levels, as well as with hyperglycaemia and elevated leukocyte SIRT1 mRNA., PI3K p110delta uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of juvenile myelomonocytic leukemia., Mutations in PIK3CD can cause hyper IgM syndrome (HIGM) associated with increased cancer susceptibility., The p110delta PI3K-selective compound CAL-101 (Idelalisib) did not inhibit markers of PI3K activity in cancer or stromal cells., Patients with activated phosphoinositide 3-kinase delta syndrome (mutation in PIK3CD) develop B-cell lymphomas., These results collectively indicate that inducible PI3Kdelta plays a crucial role in persistent activation of PI3K-Akt in fibroblast-like synoviocytes, and in the formation of a hypertrophic synovial lining., Data indicate a series of quinolinylpurines as potent and selective PI3Kdelta kinase inhibitors with in vivo efficacy as measured by two rodent disease models of inflammation and autoimmune disease., Expression of functional S1PR1 is reduced by B cell receptor signaling and increased by inhibition of PIK3CD but not SYK or BTK in chronic lymphocytic leukemia cells., work identifies FAK as a target of p110delta PI3K that links RhoA with PTEN and establishes for the first time that PTEN is a substrate of FAK-mediated Tyr phosphorylation, Combined PI3K/Akt and Hsp90 targeting synergistically suppresses essential functions of alloreactive T cells and increases Tregs., Studies indicate that phosphatidylinositol-45-bisphosphate 3-kinase 110 kDa catalytic subunit (PIK3CD p110delta) have been described (N334K, C416R, E525K and E1021K with the majority of cases carrying E1021K) as a cause for primary immunodeficiency., study concludes that activating mutations in PIK3CD may cause immunodeficiency in patients with a complex phenotype combining defective B and T cell responses, but are less likely to be discovered in patients where only the humoral arm of the immune response is affected and naive T cell numbers are normal, Impaired signaling and protein synthesis through the PI3K catalytic subunit p110delta is an underlying molecular defect and potential treatment target in select autism spectrum disorders.,
OMIM_DISEASE Immunodeficiency 14,
SP_COMMENT catalytic activity:ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate., pathway:Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis., PTM:Autophosphorylation on Ser-1039 results in the almost complete inactivation of the lipid kinase activity., similarity:Belongs to the PI3/PI4-kinase family., similarity:Contains 1 PI3K/PI4K domain., subunit:Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunit. Interacts with ERAS., tissue specificity:Expressed predominantly in leukocytes.,
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3CG) Related Genes Homo sapiens
CHROMOSOME 7,
CYTOBAND 7q22.3,
ENSEMBL_GENE_ID ENSG00000105851,
GENERIF_SUMMARY PI3K promotes assembly of adherens junctions, which, in turn, control p38 MAPK activation and enterocyte differentiation., activates phosphatidylinositol 3 (PI3) kinase and requires PI3 kinase to regulate the cell cycle [TEL/platelet-derived growth factor receptor beta], PI3K inhibits HIV-1 transcription by targeting the viral protein Tat activation complex., data indicated that the v-Crk-induced activation of PI3K/AKT pathway was cooperatively achieved by two distinct interactions, CB(1)-induced ERK activation was mediated by PI3K(IB) and this effect may have important consequences in the control of cell death/survival decision., Bordetella pertussis infection of human monocytes resulted in a marked recruitment of cellular PI3-K to the sites of B. pertussis contact, Down-regulation of PIK3CG by CpG hypermethylation is associated with progression of colorectal cancer, higher protein levels of the PI3K subunit p110 in neutrophils from MDS patients, These results indicate that PI3k/Akt pathway is involved in the signaling cascade of glioma cells required to induce cell migration., regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages, PI3-K activation is signaled by rapid feedback amplification that involves P2Y(12) receptor-mediated activation of Syk., migrating glioma cells activate the PI3-K survival pathway, protecting migrating cells from apoptosis, 1) the PI3K-Akt pathway plays an important role in preventing Fas-mediated apoptosis; and 2) a PI3 K inhibitor, such as LY294002, might be a useful anti-tumoral agent for gastric carcinoma, Vanadyl sulfate treatment also prolonged the insulin-stimulated activation of phosphatidylinositol 3-kinase (PI3-K)., Activation of hexosamine pathway affects glucose-induced phosphorylation of IRS-1. Impairs coupling of IRS-1 and PI 3-kinase and activativates Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway., Thus, our results identified a functional region in the IL-1R AcP required for the recruitment and activation of PI 3-kinase., PI3Kgamma appears to negatively control cardiac contractility through different signalling mechanisms [review], In Goto-Kakizaki rat soleus muscle, chronic administration of antioxidant alpha -lipoic-acid partly ameliorated the diabetes-related deficit in glucose metabolism including the enzymes Akt/PKB and PI-3 kinase., stromal cell-mediated apoptotic protection in B-lineage ALL is mediated by PI3K/mTOR and MEK via a synergistic mechanism, PI 3-kinase-initiated signaling pathway is one of the most frequently altered in head and neck squamous cell carcinoma., Amiloride enhances TRAIL-induced cytotoxicity by inhibiting phosphorylation of the PI 3-Kinase-Akt pathway-associated kinases and phosphatases., there is a previously unknown, p101-related regulatory subunit for PI3Kgamma, activation of the PI3K/Akt pathway identified as an anti-inflammatory signal that may contribute to the establishment of Salmonella typhimurium in the intestine., IL-4 > PI3K/Akt > NF-(kappa)B signaling pathways, which activate androgen receptor signaling, play an important role during the development of androgen independent prostate cancer cells., PI3-K promotes the expression of TFF3 and MUC2 and that the PI3-K pathway may play a pivotal role in intestinal goblet cell differentiation., p110gamma and p85alpha class Ia phosphoinositide 3-kinase (PI3K) subunits play roles in generating the antiapoptotic and chemoresistant phenotype associated with accelerated local tumor recurrence, Acanthamoeba castellani-mediated brain microvascular endothelial cell death is dependent on phosphatidylinositol 3-kinase, Stimulation of TNF-alpha-primed human neutrophils with fMLP results in biphasic activation of PI3K; the first phase is largely dependent on PI3Kgamma; the second phase is largely dependent on PI3Kdelta and regulates parallel activation of ROS production, the PI3-kinase/p38(MAPK)/CREB pathway contributes to the EGF activation of NF-IL6beta gene expression, the nSH2 domain of the p85 regulatory subumit is responsible for p110 regulatory contacts, and its disruption leads to constitutive p110 activity, In conclusion, erythropoietin may attenuate high glucose-induced endothelial cell apoptosis via PI-3 kinase pathway., The protein phosphorylation activity of PIK3 plays an essential role in beta-adrenergic receptor internalization and identify non-muscle tropomyosin as a cellular substrate., In human islets, activation of PPAR-gamma inhibits h-IAPP-induced islet cell apoptosis, and this action is at least in part mediated through activation of the phosphatidylinositol 3'-kinase-Akt cascade., The TGFbeta(1)-induced destabilisation of E-cadherin-mediated cell-cell adhesion involves phosphorylation of beta-catenin, which is regulated by E-cadherin adhesion complex-associated PI3-kinase and PTEN., as tumorigenesis progresses the addiction of cancers to their initiating oncogene is reduced to, at least in the case of Ras, the PI3K/AKT pathway., this specific PI 3-kinase isoform is involved in both proliferation and the apoptosis resistance associated with chronic myeloid leukemia, These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K-Nrf2 system may be a useful therapeutic strategy for PD., Results showed that inhibition of PI-3 kinase with wortmannin was accompanied by a considerably reduced expression of beta-catenin., analysis of a nuclear matrix attachment region like sequence in the last intron of PI3Kgamma, p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase have roles in oncogenic transformation, Cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons., It is concluded that PI3-kinase induces or modulates the activity of recombinant TRPV2 channels; in contrast to the previously proposed mechanism, activation of TRPV2 channels by PI3-kinase is not due to channel translocation to the plasma membrane., The phosphatidylinositol 3-kinase (PI3K) pathway promotes cancer cell proliferation and survival., These studies have revealed a novel mechanism of Trichostatin A action through derecruitment of a repressor from the Luteinizing hormone receptor gene promoter in a PI3K/PKCzeta-induced Sp1 phosphorylation-dependent manner., The acid-unfolded state of the SH3 domain adopts a partly folded conformation through nonnative long-range contacts between the dynamically restricted residues at the amyloid-forming condition., vascular endothelial growth factor expression is induced through the glucocorticoid receptor-related phosphatidylinositol 3-kinase/Akt and beta-catenin/T-cell factor-dependent pathway in human endothelial cells, These results demonstrate that estradiol positively regulates essential proteins of the IGF signalling pathway., PI3 kinase effectors PKB and PKC(zeta) are also activated by PI3 kinase in a CD14 dependent manner in lipopolysaccharides stimulated human peripheral blood mononuclear cells., PI3K and its product, PIP(3), facilitate bile acid-induced [Ca(2+)](i) responses in pancreatic acinar cells through inhibition of SERCA-dependent Ca(2+) reloading into the ER and that bile acid-induced trypsinogen activation is mediated by PI3K., We propose that PI(3)Kgamma regulates some aspects of neutrophil polarization that are relevant to movement, such as integrin-based adhesion and the accumulation of polymerized (F)-actin at the leading-edge., These data indicate that the aberrant expression of PTEN contributes to the activation of the PI3kinase/Akt pathway and its transcription factor mediators in glioma., PI 3-K signaling pathway suppresses phorbol 12-myristate 13-acetate-induced expression of p21WAF1/Cip1 in human leukemia cells, and that this effect is partly mediated by PKC zeta., This review describes the second-messenger PI3K gamma signalling pathways that are involved in immune responses relevant to the pathogenesis of rheumatoid arthritis and other inflammatory diseases., PI3K is not overexpressed in melanocytic lesions., PAR1 couples to G(i/o) in human platelets and activates phosphoinositide-3 kinase (PI3K)., Elevated and highly expressed levels in both laarge B-cell lymphoma and Hodgkin lymphoma., SCF-enhanced proliferation and invasion of KIT-positive colorectal cancer cells is achieved mainly through the PI3K/Akt pathway., phosphatidylinositol 3-kinase/Akt signaling and induces apoptosis is inhibited by energy depletion via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at Ser-794, Evidence is presented that PI3K is involved in basic fibroblast growth factor-stimulated fibroblast-collagen matrix contraction., Phosphorylated PIK3 was documented in 15/17 cytokeratin-positive breast cancer samples., Results suggest that aberrant activation of PI3K-Akt pathway may contribute to increased cell invasiveness and facilitate prostate cancer progression., Ep-CAM cross signaling with N-cadherin involves Pi3K, resulting in the abrogation of the cadherin adhesion complexes in epithelial cells., These results suggest that PLEK2 is involved in actin rearrangement in a PI 3-kinase dependent manner., In macrophages, uPA was found to activate MAP-kinase through PI3 kinase (PI3K), These results suggested that PKB enhanced DNMT1 stability and maintained DNA methylation and chromatin structure, which might contribute to cancer cell growth., mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism., These data identify a novel, PI-3K-dependent pathway by which CSF-1 directs delayed caspase activation in monocytes and thereby modulates DC differentiation., Phosphatidylinositol 3-kinase inhibition by LY294002 also enhanced TRAIL-induced apoptosis., phosphoinositide 3-kinase/Akt/eNOS, but not mitogen-activated protein kinase/ERK, signal transduction pathway may be involved in SDF-1alpha mediated migration of endothelial progenitor cells, Migratory response of freshly isolated T cells is dependent on PI3K signals provided predominantly by PI3Kgamma.t he role of PI3K in cell migration is context-dependent and diminishes during ex vivo maintenance., VEGF regulates angiopoietin-Tie2 signaling by inducing proteolytic cleavage and shedding of Tie2 via a novel PI3K/Akt-dependent pathway., IFNalpha-induced apoptosis requires activation of ERK1/2, PKCdelta, and JNK downstream of PI3K and mTOR, and it can occur in a nucleus-independent manner, thus demonstrating that IFNalpha induces apoptosis in the absence of de novo transcription., human betaARs undergo a process of intracellular sequestration that is dynamically reversed after LVAD support. Importantly, mechanical unloading leads to complete reversal in PI3Kgamma and betaARK1-associated PI3K activation., Cyclin G2 expression is modulated by HER2 signaling through multiple pathways including phosphoinositide 3-kinase, c-jun NH(2)-terminal kinase, and mTOR signaling., These data suggest that the PI3K/Akt and mTOR/p70S6K signaling pathways are essential for adipogenesis of human mesenchymal stem cells., Signal transduction pathways underlying the enhanced cell migration reveal that the IGF-I-IGFBP-VN complex stimulates a transient activation of the ERK/MAPK signaling pathway and a sustained activation of the phosphatidylinositide 3-kinase/AKT pathway., although PI3K can enhance early responses to the bacterial chemoattractant fMLP, it is not required for migration towards this chemoattractant, PI-3K/Akt signaling pathway participates in P2Y receptor-stimulated prostate cancer invasion by enhancing cell motility, rather than up-regulating MMP-2 and MMP-9 activities., These results suggest that caffeine has a cytoprotective effect due to the activation of the PI3K/Akt pathways in SH-SY5Y cells., Association of a functional missense polymorphismwith colon cancer risk in a population-based case-control study. [review], TNF-alpha overrides the G2/M checkpoint in keratinocytes and allows for some cells containing unrepaired cyclobutane pyrimidine dimers to enter the cell cycle. TNF-alpha seems to be dependent on PI3K-Akt activation., These data show that Hsp27 antagonizes Bax-mediated mitochondrial injury and apoptosis by promoting Akt activation via a PI3-kinase-dependent mechanism., Data show that in airway smooth muscle cells from asthmatics, the presence of a strong proliferative stimulus (10% FBS) reduces ERK activation resulting in a shift to the PI 3-kinase pathway., Results identify a molecular mechanism by which activated FGFR2 recruits Cbl in raft micro-domains to trigger PI3K ubiquitination and proteasome degradation, and reveal a role for PI3K/Akt in the control of osteoblast survival by FGFR2 signaling., The PI3K/Akt/mTOR signaling pathway is implicated in the development of cervical cancer., Cav-1 increases the basal and TGF-beta1-induced expression of type I procollagen by regulating two opposite signaling pathways, This study provides a direct link between the growth factor signaling pathways regulated by PI3 kinase/Akt and MAP kinases with Myc-mediated transcription., Transforming growth factor beta induces apoptosis through repressing the phosphoinositide 3-kinase/AKT/survivin pathway in colon cancer cells., The interplay between cancer cell-derived clusterin and IGF-1 may dictate the outcome of cell growth and dormancy during tumorigenic progression., tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases are regulated by phosphorylation, High NG2/MPG expression correlated with multidrug resistance mediated by increased activation of alpha3beta1 integrin/PI3K signaling and their downstream targets, promoting cell survival, High expression of PI3K and Akt are involved in proliferation, malignant transformation, invasion and metastasis of cervical carcinoma., 7-ketocholesterol-induced apoptosis has a role in phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway, GILZ is a mediator of glucocorticoid killing, and is regulated by PI3-kinase/AKT., The role of PI3K pathway activation in thyroid cancer is discussed, with a focus on recent advances., Activation of the PI3K pathway mediated cytoplasmic retention of the Wilms tumor (WTI) protein, which strongly suppressed the hTERT promoter., Interleukin (IL) 1beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/IkappaB kinase alpha pathway targeting activator protein-1, The p-EGFR, Our results also indicated that the integrin alphaVbeta3 antibody (LM609) could block the Angptl3-induced protein kinase B phosphorylation., mediates intracellular signals to regulate a variety of cellular responses and its genomic mutations and alterations underlie cancer, viral and/or bacterial infections.[review], MCL-1 expression is activated by Triiodothyronine, which increases its promoter activity by a non-genomic mechanism using the PI3-K signal transduction pathway., required for sphingosine-1-phosphate -induced endothelial cell migration through activation of Rac1, Activation of the PI3K pathway is significantly associated with adverse clinical outcome in renal cell carcinoma., Phosphoinositide 3-kinase/AKT signaling can promote AIB1 stability independently of GSK3 phosphorylation., Data show that M. bovis BCG-induced human beta-defensin mRNA expression in A549 cells is regulated at least in part through activation of signaling proteins of PKC, JNK and PI3K., None of the components in the IGF-1 pathway including IGFBP3, PI3k, and PTEN influence the relation between IRS-1 genotype and prostate cancer risk. Ther is no association between carriage of the variant IRS-1 gene and prostate cancer risk., Datas show that transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab., PIK3IP1 is an important regulator of PI3K in vivo, and its dysregulation can contribute to liver carcinogenesis, PI3K inhibition by Ly294002 alters gene expression in two breast cancer cell lines., Data show that IGF2 activates PI3K and TGFbeta signal pathways during proliferation and differentiation of chondrocytes., The role of PI3K/Akt activity and DNA-PKcs on XRCC1 expression/stabilization, was studied., DIDS-sensitive Cl- channels play a key role in the Low-density lipoprotein-induced cell proliferation of human aortic smooth muscle cells via the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1., These results suggest that the BMP-2 acts through PI3K/Akt, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the activations of beta1 integrin and contributing the migration of human chondrosarcoma cells., Endothelin signaling axis activates osteopontin expression through PI3 kinase pathway in A375 melanoma cells., A selective allosteric inhibitor of Akt kinase was used to interrogate a panel of breast cancer cell lines characterized for genetic lesions that activate PI3K/Akt signaling PI3K mutations., Gate control for cell polarization can explain how Rac can be employed for both PI3K-dependent and -independent signaling pathways coexisting in the same cell., The onset of terminal differentiation, while regulated by PI3-kinase and caspases, is not a classical apoptotic process., These findings demonstrate that HAPO induces endothelial cell proliferation through the PI-3K/Akt pathway., Glycine-extended gastrin induced signalling involves a JAK2/PI3-kinase/Akt/NF-kappaB sequence leading to COX-2 transcription., These data show that, in addition to inactivation of 4E-BP1 via hyperphosphorylation, signaling through the PI3K pathway silences 4E-BP1 gene transcription., HuR is a direct transcription target of NF-kappaB; its activation in gastric cancer cell lines depends on phosphatidylinositol 3-kinase/AKT signaling. HuR activation by this pathway has proliferative and antiapoptotic effects on gastric cancer cells., These data demonstrate that integrin/EGFR cross-talk is required for expression of Egr-1 through a novel regulatory cascade involving the activation of the PI3K/Akt/Forkhead pathway., IFN-gamma exerted a delayed suppressive effect on K(+) channels by enhancing iNOS expression and an acute stimulatory effect, which was independent of either NO pathways or phosphorylation mediated by PKA, PKG, and PI3K in renal proximal tubule cells., PDGF-mediated protection also involved the inhibition of gp120-induced release of mitochondrial cytochrome C. Our findings thus underscore the roles of both PI3K/Akt and Bcl family pathways in PDGF-mediated neuroprotection., The direct interaction of PI3Kgamma with PKCalpha forms a discrete regulatory module of N-formylmethionyl-leucyl-phenylalanine-dependent reactive oxygen species production in neutrophils., Altered insulin activation of the PI3K/Akt but not the MAPK pathway precedes and may contribute to development of whole-body insulin resistance and type 2 diabetes in men with low birth weight., NGF induces Mac-2BP expression via the PI3K/Akt/NF-kappaB pathway., These data demonstrated that cell adhesion-mediated PI3K/Akt activation could be one of the important mechanisms of resistance to genotoxin-induced cell death in differentiated epithelial cells., PI3K/Akt/mdm2 signalling pathway can be activated by doxorubicin and suppress apoptosis by promoting phosphorylation of mdm2 in a gastric cancer cell line., inhibition of the PI3K-AKT-mTOR pathway potently increases sensitivity of melanoma cells to chemotherapy, mtDNA depletion prevents detachment-induced apoptosis (anoikis) and promotes migratory capabilities onto basement membrane proteins through upregulation of p85 and p110 phosphatidylinositol 3-kinase (PI3K) subunits, which results in Akt2 activation, Results suggest that inhibition of PI(3)K is a novel mechanism which contributes to 8-prenylnaringenin activity to inhibit cancer cell survival and epidermal growth factor induced proliferation., Pim-1, but not PI3K, plays a major role in IL-5-mediated antiapoptotic signaling in eosinophils., Endometrial stathmin is linked to HIF-1alpha protein accumulation and VEGF expression through the PI3K/Akt signaling pathway and may be involved in regeneration of the endometrium during the menstrual cycle in human uterine cells., TGF-beta may facilitate airway remodelling by promoting VEGF release through the PI3K pathway, rather than via ASM cell proliferation., Data suggest that beta-hydroxy-beta-methylbutyrate (HMB) acts via ERK1/2 and PI3K, as blocking of the PI3K/Akt pathway revealed its requirement in mediating the promotive effects of HMB on muscle cell differentiation and fusion., PI3K signaling, therefore, plays a critical role in regulating protein production during VV infection, at least in part by controlling the abundance and activity of 4E-BP1., Results demonstrate that Ron plays an essential role in maintaining malignant phenotypes of colon cancer cells through regulating mutant PI3K activity., These results suggest that one mechanism of the apoptotic activity of magnolol involves its effect on epidermal growth factor receptor-mediated EGFR/PI3K/Akt signaling transduction pathways., bortezomib overcame TRAIL resistance at clinically achievable concentrations in hepatocellular carcinoma cells, and this effect is mediated at least partly via inhibition of the PI3K/Akt pathway, Snail upregulation by HRG-beta1 is mediated via the PI3K/Akt signaling pathway and Snail plays a key role in HRG-beta1 induced breast cancer cell metastasis through induction of EMT, Impaired PI3K signaling might account for the variability in the responses to ischemic preconditioning of human grafts from deceased donors., Data showed that tumor-associated matrices induced PI3K and beta1-integrin dependent Akt/PKB activity in MDA-MB-231 cells., TNFalpha facilitates the reduction of FLIP(L) protein, which is dependent on the phosphatidylinositol 3-kinase/Akt signaling., IL-6 functions in a cytoprotective manner, in part, by suppressing Bax translocation and dimerization through PI3K/Akt-mediated Bax phosphorylation., PRL up-regulated CHIT-1 expression via PTK, PI3-K, MAPK, and signaling transduction components., Results show that targeted disruption of the cell surface Cripto/GRP78 complex precludes Cripto activation of MAPK/PI3K and Smad2/3 pathways., the formation of LAT-mediated complexes do not appear to depend on PI3K activity, whereas the optimal downstream function of these complexes requires the catalytic function of PI3K, The authors find that the induction of NF-kappaB and phosphatidylinositol 3-kinase activities following HCMV infection was required for the initiation of monocyte-to-macrophage differentiation., dysregulation of the phosphoinositide 3-kinase/Akt/PTEN pathway is relevant to the prognosis in node-negative breast carcinoma, PTEN modulated VEGF-mediated signaling and affected tumor angiogenesis through PI3K/Akt/VEGF/eNOS pathway., Increased expression of PI3K is associated with gallbladder adenocarcinoma., Similar to its function in T cells, CEACAM1 may act as an inhibitory B cell coreceptor, most likely through recruitment of SHP-1 and inhibition of a PI3K-promoted activation pathway., PI-3 kinase activity is necessary for ERK1/2-induced disruption of mammary epithelial architecture, Loss of PTEN function in breast cancer can occur either by mutation or reduction of PTEN expression in almost half of sporadic breast tumors., inhibition of phosphatidylinositol-3 kinase (PI3K) reversed phospholipid transfer protein -induced increase in levels of GSK3 beta phosphorylated at serine 9, The constitutive activation of the PI3K-Akt pathway in Fanconi anaemia cells upregulates the expression of IL-1beta., Results show that this unique and specific bacterial entry process is dependent on the cooperation and activation of Rho family GTPase Cdc42, PI3K, and Akt., Targeting NRAS alone or both BRAF and CRAF in combination or both BRAF and PIK3CA together showed delay in tumor growth., The EGF/PI3K/STAT3 signaling is identified as an essential pathway regulating VEGF and leptin expression in EGF-responsive colon cancer cells., Asef and APC function downstream of HGF and PI3-kinase, and play critical roles in growth factor-mediated regulation of cell morphology and migration, Data show that IL-4 receptors are functionally competent in pancreatic beta-cells and that they signal via PI3K and JAK/STAT pathways., Data indicate that PI3K inhibitor, LY294002, almost completely blocked Lf(Fe(3+))-induced Akt activation, and prevented the cytoplasmic localization of p27(kip1)., Results provide evidence for the potential application of roscovitine/wormannin combination in clinical cancer treatment by repressing PI3K/Akt pathway., p110gamma activity plays an important role in maintaining a membrane-docked, readily releasable pool of secretory granules in insulinoma and human beta-cells, Data show that inhibition of NF-kappaB or PI3K potently enhanced cisplatin cytotoxicity in cells with endogenous or genetically induced low MKP1 levels., Studies indicate inhibition of the PI3K/AKT/mTOR pathway is not only a potential first-line therapeutic strategy in ovarian cancer but also could be used in recurrent disease as a means of reversing acquired chemotherapy resistance., Results demonstrated that the inhibition of spontaneous B cell apoptosis by CpG DNA was correlated to up-regulation of Bcl-xL, IAP and down-regulation of p53 and caspase 3 mediated through PI3K/AKT signaling., Data provide a basis for rational combination of MEK and PI3K inhibitors in basal-like cancers with both intact and deleted PTEN., Data elucidate a novel signaling network that leads to increased IL-8 production through p38 mitogen-activated protein kinase-dependent phosphatidylinositol 3-kinase activation in response to proteasome inactivation., over-expression of DIXDC1 might target p21 and cyclin D1 to promote colon cancer cell proliferation and tumorigenesis at least partially through activation of the PI3K/Akt pathway., Mal specifically connects TLR2/6 to PI3K activation, PIP(3) generation and macrophage polarization., Data show that IGFBP-3 is regulated by the PI3-kinase/AKT and MAPK/ERK1/2 pathways., Data show that aberrant expression of ErbB2, ErbB3 and ErbB4 in the two resistant cell lines, suggesting the existence of an autocrine loop leading to constitutive activation of MAPK and PI3K/Akt survival pathways., Results show interaction between CCR7 and its ligand CCL19 induces phosphorylation of mTOR and its target p70s6k. This phosphorylation is abolished by inhibition of CCR7 and PI3K/Akt, indicating that mTOR is involved in the CCR7-PI3K cascade., Data suggest an interaction between COX-2 enzymatic activity and PI3Kinase/AKT signaling pathway in EOC., Data show that with SF1126 treatment, caspase 3 and PARP proteins were cleaved, survivin was down-regulated, and inhibition of PI3-kinase was confirmed by reduced phosphorylation of Akt., PI3Kgamma regulates tumor cell adhesion through activation of CXCL12., Results suggest that bFGF increases the Mg(2+)](i) from the intracellular Mg(2+) stores through the tyrosine kinase/PI3K/PLCgamma-dependent signaling pathways., The gene copy number of PIK3CA is frequent genetic alteration that contributes to MCL progression. PIK3CA is a promising therapeutic target in MCL., These results identify nNOS as a target gene of a novel RA/PI3K/Akt/DAX1-dependent pathway in human neuroblastoma cells, These data indicate PI3Kgamma is an important regulator of fibroblast-mediated joint destruction in rheumatoid arthritis., These findings identify TAPP2 as a novel link between PI3K signaling and the cytoskeleton with potential relevance for leukemia progression, AP-1 activity in prostate cancer cells mediates EGF-R and PI3K signalling, is essential for their proliferation, and confers protection against radiation-induced cell death, Studies provide models for Ras in association with Raf kinase, RalGDS and PI3Kalpha and PI3Kgamma., Data show that B[a]PDE increases cyclin D1 expression, and activate the PI3-kinase/Akt/MAPK- and p70s6k pathway in Beas-2B bronchial epithelial cells., Data show that stimulation of HIF-1alpha transcription by the ND6 mutation was mediated by overproduction of reactive oxygen species (ROS) and subsequent activation of phosphatidylinositol 3-kinase (PI3K)-Akt and protein kinase C (PKC) signaling pathways., Data suggest that investigation of the mechanisms of abnormal RAS and phosphoinositide-3 kinase pathway activation in erythroblasts may contribute to the understanding of the molecular pathogenesis of PV., BMP-2 promotes motility and invasion of gastric cancer cells by activating the PI-3 kinase/Akt signal pathway., Data show that RNA silencing of choline kinase in HeLa cells completely abrogates the high concentration of phosphocholine, which in turn decreases phosphatidylcholine, phosphatidic acid and signaling through the MAPK and PI3K/AKT pathways., Oscillatory shear stress induces osteoblast-like cell proliferation through activation of alpha(v)beta(3) and beta(1) integrins and synergistic interactions of FAK and Shc with PI3K, leading to the modulation of ERK and Akt/mTOR/p70S6K pathways., The key signaling molecules in the PI3K signaling cascade, the abnormalities known to occur in thyroid cancer, and the potential for therapeutic targeting of PI3K pathway members are discussed., Data show that DAB2IP is a potent growth inhibitor by inducing G(0)/G(1) cell cycle arrest and is proapoptotic in response to stress, and that DAB2IP can suppress the PI3K-Akt pathway and enhance ASK1 activation leading to cell apoptosis., Elevated expression of p53-R175H mutant may exert gain-of-function activity to activate the EGFR/PI3K/AKT pathway and thus may contribute to the invasive phenotype in endometrial cancer., Hepcidin mRNA expression in vitro is highly sensitive to the presence of serum factors and PI3 kinase inhibition and parallels TfR2 expression, Data show 5-HT can induce activation of two interrelated signaling pathways, Erk1/2 and PI3K/Akt to induce proliferation, migration, and differentiation., Data show that the cleavage of MST1 is inhibited by the phosphatidylinositol 3-kinase/Akt pathway., Data show that suppression of PUMA through the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/p53 axis in the intestinal stem cells as a novel molecular mechanism of growth factor-mediated intestinal radioprotection., Increased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells., Genetic and biochemical analysis of these "hot-spot" mutations in human p110alpha, is reported., These data elucidate the role of PLCgamma1 in FGF-2 signalling in human umbilical vein endothelial cells demonstrating its key role in FGF-2-dependent tubulogenesis., Data show that c-mip interacts with the p85 subunit of PI3 kinase and inactivates Lck, which results in Erk1/2 and p38 MAPK activation., Heat shock protein 70 (Hsc70) plays a significant role in vascular endothelial cells via the phosphatidylinositol 3-kinase/Akt pathway., Studies indicate that the PI3K/Akt/mTOR pathway plays a critical role in breast cancer development and resistance to traditional anti-tumor strategy., genomic alterations in the Ras-PI3K pathway are widespread in endometrial carcinomas, regardless of the type of genomic instability, Data show that PI3K activation and PIP3 production lead to recruitment of the PKB/beta-arrestin/PDE4 complex to the membrane via the PKB PH domain, resulting in degradation of the TCR-induced cAMP pool and allowing full T-cell activation to proceed., The PI3K/Akt pathway may play an inhibitory role in inflammatory mediators-induced human vascular smooth muscle cell calcification through regulating alkaline phosphatase expression., These results indicate that human nasal airway fibroblasts strongly induce BLyS-expression and production by poly(I, Data report that activation of P2Y(2) receptors by extracellular UTP inhibits the IGF-I-induced p110alpha-PI3K activation., Data show that the expression of tenascin-C is induced in immune myeloid cells, and its synthesis is transcriptionally regulated and requires the specific activation of AKT/PI3K and NF-kappaB signaling pathways., phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination, molecular cross-talk between the MKP-1, p38 MAPK and PI3K pathways promotes resistance to PI3K inhibitors in hilar cholangiocarcinoma cells., These results suggested that although hypercholesterolemic serum could not change the expression of ZO-1, it could change the distribution and increase the permeability in endothelial cells through PI3K signaling pathway., The activation of the PI-3K/mTOR/translational pathway is important for IFNgamma-mediated VEGF expression in retinal pigmented epithelial cells., PI3-kinase exerts a major morphogenetic impact in simple cultured epithelia through preservation of cell height., Activation through CD160 leads to PI3K-dependent chronic lymphocytic leukemia protection from spontaneous in vitro apoptosis, as well as cellular activation with cell cycle progression and cytokine production., Data indicate that compound 26 (PKI-587) has shown excellent activity as highly efficacious PI3K/mTOR inhibitor., Data show that each of the five domains of phosphoinositide 3-kinase gamma is capable of binding anionic phospholipids to varying degrees, depending on the charge of the anionic substrate., PI3K/Akt prevents the malignant phenotype of HCT-116 colorectal cancer cells., Data show that significant expression of PI3Kgamma in neuroblastoma patient biopsies and tumor cell lines was detected., Data show that the coexpression of HSP90 with PI3K-p110alpha or expression of HSP90 along with PTEN loss has a potential as a molecular prognostic marker to predict early relapse in patients with invasive breast cancers., AR mediates EGF- and bFGF-induced colon cancer cell proliferation by activating or expressing G(1)-S phase proteins such as E2F-1, cdks, and cyclins through the reactive oxygen species/phosphoinositide 3-kinase/AKT pathway., PDK1 with AKT1 is sufficient for pathway activation independent of membrane localization and phosphatidylinositol 3 kinase, Data identify DEAF1 as an interactor and in vitro substrate of GSK3A and GSK3B that interacts with the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway., These results suggest that deregulation of the PI3K pathway in the bronchial airway epithelium of smokers is an early, measurable, and reversible event in the development of lung cancer., prostate cancer cell lines differentially express phosphoinositide-3 kinase (PI3K) catalytic subunit isoforms and dedicator of cytokinesis 2, Angiotensin II increased Akt phosphorylation and PI3K activity in cultured hypertrophic scar fibroblasts in a dose- and time-dependent manner., These findings suggest that angiotensin II plays a role in the growth of angiotensin II type I receptor-positive breast cancer cells through PI3-kinase/Akt pathway activation., PI3K might play a role in silica-induced DNA double strand break repair by regulating the expression levels of Ku70 and Ku80 in lung fibroblasts., PI3K-PKB-mTOR signaling plays a crucial role in the development of functional CD34-derived myeloid Dendritic cells, Increased PI3K is associated with multiple myeloma., Data demonstrate that PI3K/Akt pathway regulates the expression of DNMT3B at transcriptional and post-transcriptional levels, which is particularly important to understand the effects of PI3K/Akt and DNMT3B on hepatocarcinogenesis., Data suggest that the induction of apoptosis by tanshinone I in leukemia cells is mainly related to the disruption of Deltapsim, inactivation of PI3k/Akt signaling pathway, upregulation of Bax expression, and the activation of caspase-3., The phosphorylation of Thr159 in Vps34 is a key regulatory mechanism that controls the class III PtdIns3 kinase activity in cell-cycle progression, development, and human diseases including neurodegeneration and cancers., Role of germ line genetic variations in the PI3K-AKT-mTOR pathway genes as predictors of bladder cancer metastasis and invasiveness., PDCD4 regulates TRAIL sensitivity in gastric cancer cells by inhibiting the PI3K/Akt signaling pathway., The activated PI3K/Akt/COX-2 signal transduction pathway was found to be the main cause for decline in radiosensitivity in HeLa cells., The bFGF-FGFR1-PI3K-Rac1 pathway in the bone microenvironment may have a significant role in the invasion and metastasis of Ewing sarcoma., Collectively, these data suggested that, in oral epithelial cells, the herpes simplex virus 1-induced PI3K/Akt activation was involved in the regulation of apoptosis blockage and viral gene expression., Studies indicate that targeting the deregulated PI3K/PTEN-Akt signaling axis has currently emerged as one of the major tenets in anticancer drug development., Our study suggests that the type III PI3 kinase integrates diverse signals to regulate cellular levels of autophagy, and that autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner., Data indicate that stathmin is a target of the PI3K/Akt pathway in cervical cancer cells., The results above collectively show that C/EBPepsilon participates in all-trans retinoic acid induction of PI3Kgamma., FOXO3a is in a constant inactive state due to its cytoplasmic localization, and that neither PI3K/Akt nor extra-signal-regulated kinase-specific inhibition resulted in its nuclear translocation., demonstrate that alphaVbeta3 ligation results in sustained increases of PI3 kinase/Akt-dependent binding of transcription factor NF-kappaB to DNA., Bile salt-induced hepatocyte apoptosis is partly mediated via a PI3K p110gamma dependent signaling pathway, potentially involving JNK., Phosphoinositide-3-kinase gamma plays a major role in the induction of chemotaxis in platelet-activating factor-stimulated human eosinophils., VEGFR1 contributes to E. coli K1 invasion of human brain microvascular endothelial cells through the phosphatidylinositol 3-kinase/Akt signaling pathway., These findings demonstrated that PI3K-mediated actin rearrangements are required for Cronobacter sakazakii invasion of human brain microvascular endothelial cells., An inhibitor of PI3K (LY294002) blocked HSV-1 entry and the blockage was cell-type- and viral glycoprotein gD receptor-independent., levated PI3K pathway activity in acute myelogenous leukemia, Studies indicate that molecular mechanisms underlying phyagocyytossis are starting to point to the interplay between two families of crucial proteins, Platelet migration was stimulated by SDF-1 through PI3 kinase dependent mechanism., These results show that PI 3-kinase regulation of mRNA stability, predominantly mediated by BRF1, plays a major role in regulating gene expression., C. jejuni activates a PI3K/Akt-dependent anti-inflammatory pathway in human intestinal epithelial cells., Data demonstrate an important role for the PI3-kinase-Akt pathway in intracellular transport of surfactant protein A receptor P63., Data show an in vitro link between phosphoinositide 3-kinase-mediated HOXA9/HOXA10 expression, and a drug-resistant, progenitor cell phenotype in MGMT-independent pediatric glioblastoma., Findings show that oncogenic factors activating the phosphoinositide 3-kinase/Akt pathway can regulate alternative splicing of Casp9 via a coordinated mechanism involving the phosphorylation of SRp30a., PI3K-PDK1 signaling is essential for viability, MALT1 protease activity, and NF-kappaB activation in activated B-cell-like diffuse large B-cell lymphoma cells that carry mutations in the BCR proximal signaling adaptor CD79B., This indicates that not only MAPK activation, but PI3Kgamma protein kinase activity in general is localized in the cytosol., Data demonstrate that AG/UAG attenuation of ISO-induced lipolysis involves PI3Kgamma/AKT and PDE3B., p110gamma anchors protein kinase A (PKA) through a site in its N-terminal region. Anchored PKA activates PDE3B to enhance cAMP degradation and phosphorylates p110gamma to inhibit PIP(3) production, Once activated, p110gamma promotes inside-out activation of a single integrin, alpha4beta1, causing myeloid cell invasion into tumors., PI3Kgamma, a PI3K isoform exhibiting restricted tissue distribution, is strictly required for signaling from the KSHV-encoded vGPCR oncogene to Akt/mTOR., Activation of the PI3K/Akt/mTOR pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder., role of p110gamma as a promoter of HCC proliferation and unveil an important cell cycle regulation function of this molecule., our study reveals a novel link between NF-kappaB and PI3K/Akt and establishes c-FLIP as an important regulator of FasL-mediated cell death., Ras-p110gamma interaction is necessary for efficient beta-selection-promoted proliferation but is dispensable for the survival or differentiation of thymocytes., protection from insulin resistance, metabolic inflammation, and fatty liver in mice lacking functional PI3Kgamma is largely consequent to their leaner phenotype, A novel regulatory role of p101 in the activation of PI3Kgamma., The expression levels of PI3K protein and mRNA in esophageal squamous cell carcinoma tissues are significantly increased and PI3K plays a role in the carcinogenesis and development of ESCC., findings suggest that PIK3CG function impacts the severity of the intraparenchymal bleed in patients with intracerebral hemorrhage, Culturing spermatogonia in vitro at 37 degrees C could inhibit the expression of PI3K and c-kit, and lead to the mutation of the c-kit gene., a novel mechanism that links PI3Kgamma activity with chemotaxis and superoxide production in G-protein coupled receptor signaling., PI3Kgamma plays a key role in ipopolysaccharide-induced ROS generation in alveolar epithelial cells, thereby activating NF-kappaB, PI3K/AKT/mTOR signalling components appear to be differentially implicated in urothelial tumorigenesis and, with the exception of p85aPI3K, are unrelated to the PIK3CA or AKT1 mutational status., Class II enzyme PI3K-C2beta and class IB isozyme p110gamma mainly regulate the S1P- and high density lipoprotein (HDL)-dependent endothelial cell (EC) migration and PI3K-C2alpha primarily controls EC survival, kinase-independent function of PI3Kgamma could directly inhibit GSK-3 function by preventing the PP2A-PPMT-1 interaction and that this inhibition of GSK-3 was independent of Akt., Assessed the expression of class I PI3K p110 isoforms in idiopathic pulmonary fibrosis lung tissue as well as in tissue-derived fibroblast cell lines., Upregulated phosphoinositide 3-kinase gamma is a target to suppress breast cancer cell migration and invasion., Ablating the interaction of PI3Kgamma with Gbetagamma heterodimers attenuates signaling, chemotaxis, and transformation driven by a GPCR agonist in cell lines., PI3Kgamma plays an important role in the development of eosinophilic inflammation a, Binding of the HSV-1 envelope initiates the epidermal growth factor receptor EGFR-PI3K signaling pathway, which leads to virus-induced early cofilin phosphorylation and F-actin polymerization., The data indicate that PI3Kgamma has a critical role in cAMP-mediated inflammatory hypernociception and analgesic signalling via mu-opioid receptors and PI3K/Akt in neuronal cells., Data indicate class of benzothiazoles as inhibitors of phosphoinositide 3-kinase gamma., phosphatidylinositol 3-kinase gamma has a role in insulin secretion induced by glucose-dependent insulinotropic polypeptide, PI3Kgamma-induced VEGF expression was reduced when the human tocopherol-associated protein 1 (hTAP1/SEC14L2) was overexpressed suggesting formation of an inactive PI3Kgamma/hTAP1 heterodimer., The interaction between PI3Kgamma and CNGA1 does not appear to play a role in regulation of CNG channel activity, but PI3Kgamma uses CNGA1 as an anchoring module to achieve close proximity to its substrate to generate D3-phosphoinositides, increased susceptibility of individuals with COPD to influenza likely results from impaired antiviral responses, which are mediated by increased PI3K-p110alpha activity., Our findings suggest that p84 binding to p110gamma may represent a novel negative feedback signal that terminates PI3Kgamma activity., Mfng is an oncogene acting through Notch-mediated induction of Pik3cg., findings suggest that miR-502 functions as a tumor suppressor in HCC via inhibition of PI3KCG, supporting its utility as a promising therapeutic gene target for this tumor type, data argue for differential regulatory functions of the non-catalytic subunits and a specific Gbetagamma-dependent regulation of p101 in PI3Kgamma activation., Findings suggest the pathophysiological role of phosphoinositide 3-kinase gamma (PI3Kgamma) in atherogenesis., Diminished expression of p110gamma in pulmonary vascular endothelial cells of patients with acute respiratory distress syndrome suggests that impaired p110gamma-FoxM1 vascular repair signaling is a critical factor in persistent leaky lung microvessels in ARDS.,
SP_COMMENT catalytic activity:ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate., enzyme regulation:Activated by both the alpha and the beta-gamma G proteins., function:3-phosphorylates the cellular phosphoinositide PtdIns-4,5-biphosphate (PtdIns(4,5)P2) to produce PtdIns-3, 4,5-triiphosphate (PtdIns(3,4,5)P3). Links G-protein coupled receptor activation to the secondary messenger PtdIns(3,4,5)P3 production., pathway:Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis., similarity:Belongs to the PI3/PI4-kinase family., similarity:Contains 1 PI3K/PI4K domain., subunit:Heterodimer of a catalytic subunit (PIK3CG/p120) and a regulatory (PIK3R5a/p101) subunit., tissue specificity:Pancreas, skeletal muscle, liver and heart.,
phosphoinositide-3-kinase regulatory subunit 1(PIK3R1) phosphoinositide-3-kinase regulatory subunit 1(PIK3R1) Related Genes Homo sapiens
CHROMOSOME 5,
CYTOBAND 5q13.1,
ENSEMBL_GENE_ID ENSG00000145675,
GENERIF_SUMMARY Thus, the Met-326Ile variant of p85alpha is functional for intracellular signaling and adipocyte differentiation but has small alterations in protein expression and activity that could play a role in modifying insulin action., Expression of a mutated in a Hodgkin's lymphoma-derived cell line; the first detection in human hematopoietic cells further underlining a potential role of PI3-kinase/Akt signaling in human leukemogenesis, The p85 subunit of PI 3-kinase mediates GPIb-related activation signals and activates Src independently of the enzymatic activity of PI 3- kinase., Gene expression of full-length p85alpha is increased in skeletal muscle from type 2 diabetics, this is not reflected by increased protein. Defects in PI 3-kinase activity are likely due to impaired activation of the enzyme., The isoleucine variant of codon 326 of the p85alpha subunit of PI3-K might be associated with decreased risk of Prostate Cancer., p55gamma binds to Rb and modification of this association can lead to cell cycle arrest, protein whose expression is deregulated in the epidermis of the elderly., the role of p85-ALPHA in the survival of cancer cells that express wild-type PTEN, a triple complex between AR, p85alpha, and Src is required for androgen-stimulated PI3K/Akt activation, PI3K has a novel role as a bikunin target gene on uPA up-regulation and invasion, These findings reveal key events of the phosphatidylinositol 3-kinase pathway that play distinct roles to maintain tissue polarity and that when disrupted are instrumental in the malignant breast tumor phenotype., coupling of Gab1 to PI3K is important for biological responses in RET-expressing cells, Data suggest that SLP-76 may play a role in signaling pathways by interacting with the p85 subunit of phosphoinositide 3-kinase (PI3K)., p110gamma and p85alpha class Ia phosphoinositide 3-kinase (PI3K) subunits play roles in generating the antiapoptotic and chemoresistant phenotype associated with accelerated local tumor recurrence, PI3K regulates cell cycle progression and cell proliferation in human gastric tumor cells via Rb-mediated pathway; effect mediated through direct association with Rb via N-terminal end of its p55 kDa regulatory subunits and modulating Rb-E2F interactions, WAVE3-mediated migration in MDA-MB-231 cells via lamellipodia formation is activated downstream of PI3K and induced by PDGF, calcium activates PLC-gamma1 via increased PIP3 formation mediated by c-src- and fyn-activated PI3K, the nSH2 domain of the p85 regulatory subumit is responsible for p110 regulatory contacts, and its disruption leads to constitutive p110 activity, Inhibitors may provide an alternative route to effective PI3K pathway inhibition for breast cancer treatment., the signals induced by integrin alpha6beta1 modulate at the level of PI3K and Cdc42 activity to allow platelets to actively form filopodia, CD21 activation triggered Cbl tyrosine phosphorylation, which interacts with SH2 domains of p85 subunit, SH2 domains of Crk-L and with tyrosine phosphorylated Syk kinase. CD21 activation triggers dissociation of Cbl-Vav complex., SHP-2 recruitment to p85 is required for IGF-I-stimulated association of the p85/p110 complex with insulin receptor substrate-1 and for the subsequent activation of the PI-3 kinase pathway leading to increased cell migration, the PI3-K pathway negatively regulates TGF-beta/Smad signaling in neuroblastoma cells, increased expression of p85alpha may be one of the earliest molecular alterations in the mechanism of the insulin resistance associated with overfeeding, MyD88 bridges TLR5 engagement to PI3K activation in response to flagellin, Gab1 thus appears as a primary actor in coupling VEGFR-2 to PI3K/Akt, recruited through an amplification loop involving PtdIns(3,4,5)P3 and its PH domain, Hsp90 inhibition transiently activates Src kinase and promotes Src-dependent p85 PI3K and Akt and Erk activation, direct interactions between native Syk and PI3K proteins are differentially regulated during FcgammaR phagocytosis and endocytosis., It has recently been shown that Akt activation is associated with a worse outcome among endocrine treated breast cancer patients and that it also inhibits the progesterone receptor (PR) expression via the PI3K/Akt pathway in breast cancer cells., autotaxin induces uPA expression via the Gi-PI3K-Akt-NF-kappaB signaling pathway that might be critical for autotaxin-induced tumor cell invasion and metastasis, Association of single nucleotide polymorphisms with serum leptin and body fat may reflect a diminished ability of this enzyme to signal in ersponse to leptin., constitutively active Stat5 mutant forms a complex with the p85 subunit of phosphatidylinositol 3-kinase and the scaffolding adapter Gab2 in leukemic bone marrow cells, resulting in the activation of Akt/PKB, a crucial downstream target of PI3-K, hypothesized that variants in the SHP-2 gene PTPN11 and PI3K p85alpha subunit gene PIK3R1 may influence fasting levels of plasma apoB and/or LDL cholesterol, the WASp/SNX9/p85/CD28 complex enables a unique interface of endocytic, actin polymerizing, and signal transduction pathways required for CD28-mediated T cell costimulation, the recruitment of PI3K to the E-cadherin/beta-catenin/p120-catenin complex via beta-catenin at the plasma membrane is required for calcium-induced phospholipase C-gamma1 activation and, ultimately, keratinocyte differentiation, PI3K is not overexpressed in melanocytic lesions., These results indicate that the phosphatidylinositol 3-kinase/Akt/FoxO1 pathway participates in Ang II suppression of hSR-BI/CLA-1 expression and suggests that the endothelial receptor for hSR-BI/CLA-1 is downregulated by the renin-angiotensin system., These results support a model in which phagosomal PI3K generates PI(3,4,5)P(3) necessary for later stages of phagocytosis, PTEN determines whether those late stages can occur, and SHIP-1 regulates when and where they occur., PKC alpha may be associated with regulation of cell proliferation/migration/invasion in human poorly differentiated hepatocellular carcinoma cells, RhoG protects cells from apoptosis caused by the loss of anchorage through a PI3K-dependent mechanism, independent of its activation of Rac1, IGF-1 activates the IGF receptor/IRS/PI3K/PKB pathway, and that PI3Kalpha is essential for the potentiatory effect of IGF-1 on platelet responses, Endothelial cell PI 3-kinase activity and F-actin remodeling are required during lymphocyte diapedesis and identify a PI 3-kinase-dependent step following initial separation of the VE-cadherin barrier., study reports a 3.0 angstrom resolution structure of a complex between p110alpha and a polypeptide containing the p110alpha-binding domains of p85alpha; results suggest specific mechanisms for the effect of oncogenic mutations in p110alpha and p85alpha, PI3K is activated by toll-like receptor stimulation in primary human plasmacytoid predendritic cells (pDCs), and it is required for type I IFN production by pDCs, both at the transcriptional and protein levels, Binding of CD95 Ligand to CD95 on glioblastoma cells recruit Yes and the p85 subunit of phosphatidylinositol 3-kinase to CD95, which signal invasion via the glycogen synthase kinase 3-beta pathway and subsequent expression of matrix metalloproteinases., p85alpha and p110beta are essential for androgen-stimulated AR transactivation, and their aberrant expression or activation might play an important role in prostate cancer progression, structure of the complex between the catalytic subunit of PI3Kalpha, p110alpha, & a portion of its regulatory subunit, p85alpha reveals the majority of the oncogenic mutations occur at the interfaces between p110 domains & between p110 & p85 domains, the influenza A virus NS1 protein interacts with the p85beta, but not the p85alpha, subunit of phosphatidylinositol 3-kinase, caspase 8 has a role as a modulator of p85alpha Rab5-GAP activity and endosomal trafficking, ARF1 regulates epidermal growth factor-dependent breast cancer cell growth and invasion during cancer progression by controlling the activation of the phosphatidylinositol 3-kinase pathway, The PI3-kinase gene Met326Ile polymorphism may not be a major determinant for the development of polycystic ovary syndrome (PCOS), but it may modulate the concentrations of serum 17-OHP or free testosterone in PCOS patients., FGFR3 and p85 proteins interact in myeloma cells which express p85alpha and p85beta., Abnormal PI3K p85alpha expression occurs in the progression of colorectal cancer in close relation to the clinical stage., p85alpha and p85beta may recruit proteins in the endocytic machinery on Epo stimulation; mutated EpoRs from primary familial and congenital polycythemia patients lacking the 3 important tyrosines do not bind p85 or internalize on stimulation, an interaction between the regulatory subunit of PI3K, p85, and the adaptor protein CrkL is required for efficient NKG2D-mediated cellular cytotoxicity, CoA synthase is involved in signaling events in the cell and forms a functional complex with p85alphaPI3K in vivo., the PIK3R1 mutation is rare in human cancers, PTEN-p85 association involves the unphosphorylated form of PTEN engaged within the PTEN-associated complex and also includes the p110beta isoform of PI3K., Our results demonstrated that shRNA targeting COX-2, Akt1 and PIK3R1 downregulates their expression significantly in a sequence-specific manner, exerting proliferation and invasion inhibition effects on SGC7901 and U251 cells, Findings indicate a novel mechanism by which hypoxia induces CD36 expression via activation of HIF-1 and the phosphatidylinositol 3-kinase pathway., Data show that mesothelin is a potential target in reducing resistance to cytotoxic drugs, and mesothelin-treated cells revealed rapid tyrosine phosphorylation of the p85 subunit of PI3K., PI3K p85alpha depletion induces cell cycle arrest and apoptosis in colorectal cancer cells, findings show presence of frequent mutations in p85alpha in colon cancer, a majority of which occurs in the inter-Src homology-2 domain; these mutations uncouple & retain p85alpha's p110-stabilizing activity, while abrogating its p110-inhibitory activity, p85alpha regulatory protein binds directly to and enhances PTEN lipid phosphatase activity, PI3Kp85alpha gene silencing can significantly promote 5-fluorouracil-induced apoptosis of colorectal LoVo cells., Results substantiate the concept that the p85 subunit of PI3K has a tumor-suppressive role in the liver and possibly other tissues., Data show that the mutations weaken an inhibitory interaction between p85alpha and p110alpha., PI-3K p85 in gestational diabetes mellitus patients may be involved in the insulin signaling pathway, resulting in insulin resistance., PIK3R1 might play a role in the pathogenesis of hypersplenism due to portal hypertension, and inhibition of PIK3R1 expression might be a novel therapeutic strategy for it., In the current study, we have shown that p85alpha, the regulatory subunit of phosphatidylinositol-3-kinase, has a critical role in mediating p53 acetylation and promoter-specific transactivation in the ultraviolet B (UVB) response., Leukemia cells can regulate the expression of p85alpha by posttranscriptional regulation., rs3756668 located in 3'-UTR of the PIK3R1 gene is associated with insulin resistant phenotype, SIRT1 interacts in an insulin-independent manner with the PI3K adapter subunit p85, lipid kinase p110beta/p85beta elucidates an unusual SH2-domain-mediated inhibitory mechanism, Single nucleotide polymorphisms in PIK3R1 is associated with prostate cancer., found that PIK3R1 was somatically mutated in 43% of endometrial cancers and 12% of nonendometrioid endometrial cancers, We did not find any mutation in the GNAQ, AKT3, and PIK3R1 genes in various types of thyroid cancer., presence of TSC2 mutations, in addition to TSC1 mutations, underlines the involvement of mTOR signaling in urothelial carcinoma, This paper reports the first purification of a phosphoinositide 3-kinase and shows that the protein is a heterodimer of an 85 kd regulatory subunit that mediates binding to phosphorylated proteins and a 110 kd catalytic subunit., Data show that mutation of serine 83 to alanine on p85 inhibited 14-3-3zeta binding to the p85 subunit of PI3K., Multiple PIK3R1 and PIK3R2 mutations demonstrate gain of function, including disruption of a novel mechanism of pathway regulation wherein p85alpha dimers bind and stabilize PTEN., PIK3R1, like PIK3CA, is a potential therapeutic target in Glioblastoma multiforme and that it also influences tumor cell growth and motility, a global conformational change in p110alpha consistent with allosteric regulation of the kinase domain by the P85 N-terminal SH2 domain, Cyclin G1 overexpression enhanced Akt activation through interaction with p85 (regulatory subunit of phosphoinositide 3-kinase), High p85alpha is associated with non-small cell lung cancer., miR-376a may contribute to the development of hepatocellular carcinoma by targeting p85alpha, Insulin stimulation promoted an interaction between the IRS1/p85 complex and PPP1R12A; however, p85 and PPP1R12A did not interact independent of IRS1., Data indicate that erufosine caused dose-dependent decreases in the phosphorylation of PI3K (p85), Akt (PKB) at Thr 308 and cRaf in both MCF-7 and MDA-MB 231 cell lines., Introduction of a subset of the mutations identified in human glioblastoma, in the nSH2 and iSH2 domains, increases signaling through the PI3K pathway and promotes tumorigenesis of primary normal human astrocytes., Both alpha and beta isomers of the PI3K regulatory subunit p85 and full-length rotavirus NSP1 are important for this interaction, which results in efficient activation of the PI3K/Akt pathway during rotavirus infection., PI3K behaves as an upstream regulator of PKCdelta and p38 MAPK in WISH cells., Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells., Data indicate PI3K p85 mediates the interaction of beta-catenin with NF-kappaB (p65)., It is a key player in cell-growth signaling in a number of lymphoid malignancies., Individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling., A heterozygous PIK3R1 mutation is observed in two unrelated families affected by partial lipodystrophy, low body mass index, short stature, progeroid face, and Rieger anomaly (SHORT syndrome)., PIK3R1 mutations are the major cause of SHORT syndrome., miR-486 directly targets components of insulin growth factor (IGF) signaling including IGF1, IGF1 receptor, and phosphoinositide-3-kinase, regulatory subunit 1alpha (PIK3R1, or p85a) and functions as a potent tumor suppressor of lung cancer., PIK3R1 de novo missense mutation (c.1945C>T; p.Arg649Trp) cause SHORT syndrome., HSP20 directly associates with PI3K subunits and suppresses its activity in hepatocellular carcinoma, resulting in the inhibition of the AKT pathway, and subsequently decreasing the growth of hepatocellular carcinoma., PIK3CA mutations and PIK3R1 underexpression show opposite effects on patient outcome and could become useful prognostic and predictive factors in breast cancer., Knockdown of RPS7 resulted in increased expression of P85alpha, P110alpha, and AKT2., These data, plus the fact that Sam68 is known to be a signaling adaptor protein, indicated that Sam68 is a signal molecule with a functional role in the PI3K/Akt signal pathway during enterovirus 71 infection., mutant forms of p85alpha may play an oncogenic role in bladder cancer, MPP3 and Dlg, membrane-associated guanylate kinase homologs (MAGuK) proteins, connect CADM1 with p85 of PI3K by forming a multi-protein complex at the periphery of cells., High PI3K p85 expression is associated with non-small cell lung cancer., BRD7-mediated translocation of a subfraction (but not all) of the p85 protein to the nucleus could enhance PI3K signaling., SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1, we report PIK3R1 as the gene implicated in SHORT syndrome in two patients., In trastuzumab-treated HER2-positive breast cancer patients, positive p85 protein expression appears to be a prognostic factor of poor survival and, if validated, might have important implications in the treatment of such patients., This study highlights the p85alpha (PI3K)S83 role as a key regulator of cell proliferation and motility induced by insulin in MCF-7 cells breast cancer model., PI3K activity is tightly regulated in T and B lymphocytes and that various defects in the PI3K-triggered pathway can cause primary immunodeficiencies., Data show that miR-221 and miR-222 repress respectively the levels of PIK3R1 and ETS1 to regulate angiogenic features in endothelial progenitor cells and endothelial cells., This study identified that CGPs was found to significantly correlate with the differential expression and methylation of genes encoding phosphoinositide-3-kinase, regulatory subunit 1., describe two neomorphic PIK3R1 mutants prevalent in endometrial and colon cancer that induce transformation via activation of PI3K-independent pathways, these data demonstrate that Pyk2 is a critical regulator of PI3K function downstream of the TCR., Data conclude that miR-486-5p, which is frequently downregulated in HCC, inhibits HCC progression by targeting PIK3R1 and phosphatidylinositol 3-kinase-AKT activation., Patients who harbor a recently reported heterozygous splice site mutation in PIK3R1 suffer from recurrent sinopulmonary infections and lymphoproliferation., genetic association studies in populations in Ireland and Belgium, Defective podocyte insulin signaling through p85-XBP1 promotes ATF6-dependent maladaptive ER-stress response in diabetic nephropathy., PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3beta/CTNNB1 signaling pathway, expression determinant of gemcitabine sensitivity in pancreatic ductal adenocarcinoma, Heterozygous splice site mutations in PIK3R1 are associated with an immunological phenotype resembling hyper-IgM syndrome, and altered germinal center reaction with abnormal B cell peripheral maturation., we conclude that miR-128-3p, which is frequently downregulated in HCC, inhibits hepatocellular carcinoma (HCC). progression by regulating PIK3R1 and PI3K/AKT activation, and is a prognostic marker for HCC patients., The synaptic recruitment of lipid rafts is dependent on CD19-PI3K module and cytoskeleton remodeling molecules., Analysis of interdomain interactions of wild-type and mutants at the p110alpha-p85alpha interface with molecular dynamics simulations suggest that tumor-associated mutations weaken interactions between p110alpha and p85alpha by disrupting key stabilizing interactions., Three of these, PIK3R1, VEGFA, and ITGB1, are known to be associated with preeclampsia or preeclampsia-related biological processes, As a consequence, homodimeric but not monomeric p85alpha suppresses the phosphatidylinositol 3-kinase pathway by protecting PTEN from E3 ligase WWP2-mediated proteasomal degradation., NOS stimulation via PI3K, calpain proteases, and SIRT1-dependent deacetylation downstream from VEGFR2 activation contributes to these vasodilator responses., study provides new insight into the structure and assembly of the p85alpha homodimer and suggests that this protein is a highly dynamic molecule whose conformational flexibility allows it to transiently associate with multiple binding proteins., A Cytosolic Multiprotein Complex Containing p85alpha Is Required for beta-Catenin Activation in Colitis and Colitis-associated Cancer., PIK3R1 knockdown abrogated antimiR21-induced effect on breast cancer cells., PI3KR1 plays a crucial role in the development of germinal center follicular helper T cells and is not involved in the generation of normal follicular regulatory T cells, RAC1/RAC2 and SFK are proximal and essential for phosphatidylinositol 3-kinase (PI3K) activation in NK cell-mediated direct cytotoxicity against Cryptococcus neoformans.,
OMIM_DISEASE SHORT syndrome, Agammaglobulinemia 7, autosomal recessive, Immunodeficiency 36,
SP_COMMENT disease:Defects in PIK3R1 are a cause of severe insulin resistance., domain:The SH3 domain mediates the binding to CBLB, and to HIV-1 Nef., function:Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues., PTM:Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation., similarity:Belongs to the PI3K p85 subunit family., similarity:Contains 1 Rho-GAP domain., similarity:Contains 1 SH3 domain., similarity:Contains 2 SH2 domains., subunit:Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunits. Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR and/or BCR activation. Interacts with SOCS7. Interacts with RUFY3 (By similarity). Interacts with phosphorylated LAT, LAX1 and TRAT1 upon TCR activation. Interacts with CBLB. Interacts with HIV-1 Nef to activate the Nef associated p21-activated kinase (PAK). This interaction depends on the C-terminus of both proteins and leads to increased production of HIV. Interacts with HCV NS5A. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with IRS1 and phosphorylated IRS4, as well as with NISCH and HCST., tissue specificity:Isoform 2 is expressed in skeletal muscle and brain, and at lower levels in kidney and cardiac muscle. Isoform 2 and isoform 4 are present in skeletal muscle (at protein level).,
phosphoinositide-3-kinase regulatory subunit 2(PIK3R2) phosphoinositide-3-kinase regulatory subunit 2(PIK3R2) Related Genes Homo sapiens
CHROMOSOME 19,
CYTOBAND 19q13.2-q13.4,
ENSEMBL_GENE_ID ENSG00000105647, ENSG00000268173,
GENERIF_SUMMARY Mutant viruses carrying NS1 with mutations in SH3 binding motif 1 failed to interact with p85ss and induce the subsequent activation of PI3K/Akt pathway., in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration, the influenza A virus NS1 protein interacts with the p85beta, but not the p85alpha, subunit of phosphatidylinositol 3-kinase, FGFR3 and p85 proteins interact in myeloma cells which express p85alpha and p85beta., p85alpha and p85beta may recruit proteins in the endocytic machinery on Epo stimulation; mutated EpoRs from primary familial and congenital polycythemia patients lacking the 3 important tyrosines do not bind p85 or internalize on stimulation, PTEN-p85 association involves the unphosphorylated form of PTEN engaged within the PTEN-associated complex and also includes the p110beta isoform of PI3K., Data show that mesothelin is a potential target in reducing resistance to cytotoxic drugs, and mesothelin-treated cells revealed rapid tyrosine phosphorylation of the p85 subunit of PI3K., NS5A mediates activation of beta-catenin in a phosphoinositide-3 kinase-dependent fashion., oncogenic p85 mutations lead to a loss of a C2-iSH2 domain contact that is required for inhibition of p110alpha by p85., the PTEN phosphatase is active against the PI3K p85beta subunit and dephosphorylates a protein involved in insulin signaling where known downstream consequences are increased cell migration, motility, and invasion., Macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85-thereby linking Abl kinase signaling to p85-dependent regulation of macropinocytosis., Overexpression of SH3 domain of p85beta inhibits influenza A virus replication., The crystal structure of human p85beta iSH2 determined to 3.3A resolution is reported., miR-126 could target both VEGFA and PIK3R2, and its expression was decreased in human breast cancer, implying that miR-126 may play a role in tumor genesis and growth by regulating the VEGF/PI3K/AKT signaling pathway, study shows that p110beta nuclear localization signal and p85beta nuclear export sequence regulate p85beta/p110beta nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110beta controls cell survival, This paper reports the first purification of a phosphoinositide 3-kinase and shows that the protein is a heterodimer of an 85 kd regulatory subunit that mediates binding to phosphorylated proteins and a 110 kd catalytic subunit., Multiple PIK3R1 and PIK3R2 mutations demonstrate gain of function, including disruption of a novel mechanism of pathway regulation wherein p85alpha dimers bind and stabilize PTEN., recombinant production, crystallization and X-ray structure determination at 2.0 A resolution of the SH3 domain of human p85beta is described, identified mutations in AKT3, PIK3R2 and PIK3CA in 11 unrelated families with megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndromes, p85beta phosphoinositide 3-kinase subunit regulates tumor progression, miR-126-mediated phosphoinositide-3-kinase regulation, not only fine-tunes VEGF-signaling, but it strongly enhances the activities of Ang-1 on vessel stabilization and maturation., Both alpha and beta isomers of the PI3K regulatory subunit p85 and full-length rotavirus NSP1 are important for this interaction, which results in efficient activation of the PI3K/Akt pathway during rotavirus infection., Data indicate PI3K p85 mediates the interaction of beta-catenin with NF-kappaB (p65)., FBXL2 mediates the ubiquitylation and degradation of p85beta on cell membranes., Study indicates that miR-126 is a tumor suppressor that inhibits gastric cancer cells proliferation by targeting PI3KR2, Crk and PLK2., the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2., The authors show that this potentiation involves reorganization of the natural CrkL-p85beta complex into a novel trimeric complex where influenza A virus NS1 serves as a bridging factor., The miR-126 was found to act as proliferation suppressor targeting PIK3R2 gene and reducing p85beta (a regulatory subunit of PI3K kinase) protein translation and lower AKT kinase activity., Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from Bilateral perisylvian polymicrogyria with a normal head size to the megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome., indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression,
OMIM_DISEASE Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1,
SP_COMMENT function:Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane., similarity:Belongs to the PI3K p85 subunit family., similarity:Contains 1 Rho-GAP domain., similarity:Contains 1 SH3 domain., similarity:Contains 2 SH2 domains., subunit:Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunits.,
phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1p34.1,
ENSEMBL_GENE_ID ENSG00000117461, ENSG00000278139,
GENERIF_SUMMARY IGF2-PIK3R3 signaling axis is involved in promoting the growth of a subclass of highly aggressive human glioblastomas that lack EGF receptor amplification., We have identified novel nonclassical mediators of the SREBP-1 response, including p55gamma, supporting the hypothesis that SREBP-1 regulates stress response and signaling genes., A fusion peptide containing the p55PIK amino terminus, TAT-N24, which not only inhibited cell proliferation, but also stimulated differentiation., PIK3R3 was up-regulated in gastric cancer and promoted cell cycle progression and proliferation., Data show that miR-7 inhibits the effects of TLR9 signaling on lung cancer cells through regulation of the PIK3R3/Akt pathway., p55PIK is transcriptionally activated by MZF1, resulting in increased proliferation of colorectal cancer cells, Containing the N24 of PI3K-p55PIK., our results show that the-PCNA interaction is important in regulating DNA synthesis and contributes to tumorigenesis., p55PIK could be a substrate of activated caspase 6 during paraquat-induced apoptosis, leading to loss of original biological functions and redistribution to disturb cell cycle progression., discovered that ERBB4 and S6K2 were the direct targets of miR-193a-3p and that PIK3R3 and mTOR were the direct targets of miR-193a-5p in non-small-cell lung cancer, study shows that the p53/miR-148b/p55PIK axis has an important role in cell proliferation and tumor growth, and may represent a novel therapeutic target for treating cancers containing p53 mutations or losses., Overexpression of PIK3R3 depends on SNAI2, inducing significant epithelial-to-mesenchymal transition (EMT)., PIK3R3, ITGB1, ITGAL, and ITGA6, were involved in the regulation of actin cytoskeleton that link to triple-negative breast cancer migration., TGF-beta/NKX2.1/PIK3R3 axis is crucial in the TGF-beta-induced inhibition of cell proliferation, and the NKX2.1/PIK3R3 axis might become a target in TGF-beta receptor-repressed lung adenocarcinoma, p55gamma sequentially up-regulated p53 and p21, resulting in cell-cycle arrest in S phase; small-interfering RNA knockdown of either p53 or p21 blocked p55gamma-induced vascular smooth muscle cell growth arrest., our findings provide new insights into tumor suppression by miR-511 by negatively regulating the PIK3R3/AKT/mTOR signaling pathway, PIK3R3 was identified as a crucial target gene of miR-132., The proliferation, migration and invasion was decreased in ovarian SKOV3 when HOTAIR or PIK3R3 was silenced.,
SP_COMMENT function:Binds to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulates their kinase activity. During insulin stimulation, it also binds to IRS-1., similarity:Belongs to the PI3K p85 subunit family., similarity:Contains 2 SH2 domains., subunit:Heterodimer of a p110 (catalytic) and a p55 (regulatory) subunits., tissue specificity:Highest levels in brain and testis. Lower levels in adipose tissue, kidney, heart, lung and skeletal muscle.,
phosphoinositide-3-kinase regulatory subunit 5(PIK3R5) phosphoinositide-3-kinase regulatory subunit 5(PIK3R5) Related Genes Homo sapiens
CHROMOSOME 17,
CYTOBAND 17p13.1,
ENSEMBL_GENE_ID ENSG00000141506,
GENERIF_SUMMARY p101 has a role in membrane recruitment and activation of PI3K gamma, analysis of functional domains in the p101 regulatory subunit of phosphoinositide 3-kinase gamma, Overexpression of p101 activates PI3Kgamma signaling and is associated with T-cell lymphomas, Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis., expression and activities of PI3Kgamma are modified differently by p87 and p101 in vitro and in living cells, arguing for specific regulatory roles of the non-catalytic subunits in the differentiation of PI3Kgamma signaling pathways., PIK3R5 promoter hypermethylation is associated with oral squamous cell carcinoma., data argue for differential regulatory functions of the non-catalytic subunits and a specific Gbetagamma-dependent regulation of p101 in PI3Kgamma activation.,
OMIM_DISEASE Ataxia-oculomotor apraxia 3,
SP_COMMENT domain:The heterodimerization region allows the binding to the catalytic subunit., enzyme regulation:Greatly activated by G gamma proteins., function:Regulatory subunit of the PI3K gamma complex., subunit:Heterodimer of a catalytic subunit (PIK3CG/p120) and a regulatory (PIK3R5a/p101) subunit. Interacts with G beta gamma proteins., tissue specificity:Highly expressed in leukocytes, followed by spleen, lymph node, thymus ans bone marrow.,