Database for Annotation, Visualization and Integrated Discovery 2.1
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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
CYTOBAND 3q26.3,
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.,