Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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mechanistic target of rapamycin(MTOR) mechanistic target of rapamycin(MTOR) Related Genes Homo sapiens
CYTOBAND 1p36.2,
GENERIF_SUMMARY The mTOR pathway is influenced by the intracellular concentration of ATP, independent of the abundance of amino acids, and mTOR itself is an ATP sensor., phosphatic acid mediated mitogen activation of mTOR signaling, Atrophy and hypertrophy of skeletal muscle are associated with decreases and increases in Ser(2448) phosphorylation, a site in the mammalian target of rapamycin (mTOR) phosphorylated by protein kinase B (PKB) in vitro., Predominant nuclear localization in normal and malignant cells in culture., Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E, Syncytia from cells expressing the HIV-1 Env gene fused with cells expressing CD4/CXCR4 undergo apoptosis after nuclear translocation of mTOR, mTOR-mediated p53 phosphorylation, p53-dependent Bax upregulation & mitochondrial death pathway activation., mTOR interacts with Raptor to form a nutrient-sensitive complex that signals to the cell growth machinery., mTOR-catalyzed phosphorylation of 4EBP1 in vitro and mTOR action in vivo require the participation of mTOR binding protein, raptor., These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR)., FRAP is a CLIP-170 kinase positively regulating the MT-binding behavior of CLIP-170, Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin; These studies position mTOR as an upstream activator of HIF-1 function in cancer cells, hamartin and tuberin function together to inhibit mammalian target of rapamycin (mTOR)-mediated signaling to eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1), mTOR substrate specificity is regulated by serine in the rapamycin binding domain, the AMPK and mTOR signalling pathways are possibly linked., raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs., mammalian target of rapamycin regulates STAT1-dependent gene transcription by lipopolysaccharide and interferon-gamma, mTOR is a critical target for survival signals generated by phospholipase D in breast cancer cells., Rheb is a mediator of MTOR., TOR-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1, Identification of domains of FRAP/mTOR which may mediate its association with the endoplasmic reticulum and the Golgi apparatus., This review describes recent progress in understanding the control of the mTOR signaling pathway and the role of mTOR-interacting proteins., K-Ras-mediated transformation of intestinal epitelial cells involves activation of the PI3K/mTOR pathway., Thr2446 as a novel nutrient-regulated phosphorylation site on mTOR, Activation of hexosamine pathway affects glucose-induced phosphorylation of IRS-1. Impairs coupling of IRS-1 and PI 3-kinase and activativates Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway., A new form of mTOR elucidates the molecular mechanism underlying mTOR-dependent regulation of RNA synthesis, PI3K mediates G(1) progression and cyclin expression through activation of an AKT/mTOR/p70S6K1 signaling pathway in the ovarian cancer cells., an intact PI3K/mTOR pathway is necessary for the ability of IFNalpha to induce apoptosis, whereas activation of the Jak-STAT pathway alone appears to be insufficient for this specific IFNalpha-induced effect, mTOR does not have a role in B-Raf kinase activity regulation by tuberin and Rheb, mTOR regulates PP5, which activates apoptosis signal-regulating kinase 1 signaling, Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress., ANG II activates rapamycin-sensitive mTOR signaling pathway in human coronary smooth muscle cells and involves activation of phosphatidylinositol 3-kinase, p70(S6k), and eukaryotic initiation factor-4E, leading to activation of protein synthesis., The rapid activation of PI3K-Akt/PKB-mTOR-p70(S6K) cascade by T3 provides a new molecular mechanism for thyroid hormone action, Human cytomegalovirus induces mechanisms to maintain the integrity of the eIF4F complex even when mTOR signaling is inhibited., PKC-eta targets the Akt and mTOR signaling pathways, stromal cell-mediated apoptotic protection in B-lineage ALL is mediated by PI3K/mTOR and MEK via a synergistic mechanism, mTOR may play a major role in IL-12-induced IFN-gamma production by activated T cells, the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose transport in 3T3-L1 and human adipocytes, identification of an alternative survival signal that is dependent on phospholipase D and mTOR and is active in a breast cancer cell line where the phosphatidylinositol-3-kinase survival pathway is not active, Review. TOR is a transducer of information from various sources, including growth factors, energy sensors, hypoxia sensors, & components regulating growth & division. Blocking TOR mimics amino acid & growth factor deprivation & has a cytostatic effect., mTOR/S6K1 overactivation contributes to elevated serine phosphorylation of IRS-1, leading to impaired insulin signaling to Akt in liver and muscle, diverse control signals converge on the mTOR-S6K1 signaling pathway, Overexpression of phospho-mTOR is associated with liver neoplasms, Subependymal giant cell astrocytoma cells show high levels of phospho-S6K, phospho-S6, and phospho-Stat3, all proteins downstream of and indicative of mTOR activation., DGKzeta-derived phosphatidic acid acts as a mediator of mTOR signaling, RTP801 and RTP801L work downstream of AKT and upstream of TSC2 to inhibit mTOR functions, An inhibitor of this and of the EGF receptor pathwway inhibits growth of glioma in a xenograft mousse model., RSPRR motif interacts with a negative regulator of S6K1 that is normally suppressed by mTOR., During recovery, the inhibition of mTOR by AMPK is suppressed, and its activation is maximized by the presence of AA., Rrapamycin inhibits fibronectin-induced vascular smooth musscle migration through a pathway that involves mTOR., results show show that target of rapamycin (TOR) kinase and its associated protein rictor are necessary for AKT/PKB Ser473 phosphorylation and that a reduction in rictor or mammalian TOR (mTOR) expression inhibited an Akt/PKB effector, S6 kinase 1 is essential for the control of muscle cytoplasmic volume by Akt and mTOR, EGF and hypoxia induce CXCR4 in non-small cell lung cancer, a process regulated by the PI3-kinase/PTEN/AKT/mTOR signaling pathway and activation of HIF-1alpha, binding of mTOR to Rheb mutants that are unable to bind guanyl nucleotide in vivo is inhibited by amino withdrawal; inhibitory effect of amino acid withdrawal is exerted through action on mTOR, at a site distinct from that responsible for binding Rheb, p70S6 kinase is a major effector of mTOR phosphorylation at Ser-2448 in response to both mitogen- and nutrient-derived stimuli, S6 kinase 1 is a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase, The mainly anti-apoptotic mTOR signalling is downregulated in cellular and transgenic models of Alzheimer's disease and in peripheral cells of patients, and could contribute to the pathogenesis of the disease., Data show that the farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling., activation of mTOR by Akt-mediated cellular energy and inhibition of AMPK is the predominant pathway by which Akt activates mTOR in vivo, hVps34 is a nutrient-regulated lipid kinase that integrates amino acid and glucose inputs to mTOR and S6K1, levels of p-mTOR (Ser2481), and p-4E-BP1 (Thr70 and Ser65) dramatically increase in Alzheimer disease, and are positively significantly correlated with total tau and p-tau, T-cad overexpression in vascular endothelial cells protects against stress-induced apoptosis through activation of the PI3K/Akt/mTOR survival signal pathway and concomitant suppression of the p38 MAPK proapoptotic pathway, phospholipase D suppresses protein phosphatase 2A and is involved in the mTOR survival pathway in the transformation of human cells, simultaneous blockade of mTOR and NF-kappaB pathways synergize to significantly inhibit or abrogate the proliferative responses of BM endothelial cells to mitogenic stimuli, A redox-sensitive mechanism regulates the phosphorylation of the raptor-mTOR effector S6K1, the interaction between raptor and mTOR, and the kinase activity of the raptor-mTOR complex., the inhibition of EGFR and mTOR has distinct as well as common signaling consequences in glioblastoma multiforme cells, the mTOR pathway plays an important role during megakaryopoiesis by regulating ploidy, cell size, and maturation, in part by regulating p21 and cyclin D3., mTOR maneuvers on and off the eukaryotic initiation factor 3 translation initiation complex., HIF1a has a role in determining sensitivity to inhibitors of mTOR in kidney cancer, Raptor directly binds to and serves as a scaffold for mTOR-mediated phosphorylation of IRS-1 on Ser636/639., mTOR nuclear import is required for its cytoplasmic signaling to S6K1, Taken together, these results demonstrate that an intact mTOR pathway is critical for IFN-gamma-induced suppression of pY-STAT3 and apoptosis., The mTOR protein activation, as measured indirectly by augmented levels of phospho-S6 protein, was more frequent in tumors with gene alterations in either EGFR or KRAS than in their wild-type counterparts., MSL complex interacts with components of the nuclear pore, in particular Mtor/TPR and Nup153. Knockdown of Mtor or Nup153 results in loss of the typical MSL X-chromosomal staining and dosage compensation in Drosophila male cells but not in female cells., eukaryotic translation initiation factor 4E binding protein 1(4E-BP1) overexpression is associated with prostate cancer, especially when combined with phosphatase and tensin homolog(PTEN) and mammalian target of rapamycin(mTOR) expression data, mTOR may have a role in increasing survival of cervical cancer patients who are treated with cisplatin-based neoadjuvant chemotherapy, The higher expressions of mTOR protein was associated with worse outcome in glioblastoma., 4E-BP1 binds to eukaryotic initiation factor-4E (eIF4E) to prevent the formation of the active translation complex and dissociates from eIF4E by phosphorylation through the mammalian target of rapamycin (mTOR) in the cells stimulated by amino acids., the mTOR pathway regulates mitochondrial oxygen consumption and oxidative capacity, Inhibition of mammalian target of rapamycin (mTOR) with rapamycin (10-100 nmol/L) had no significant effect on HIF-1alpha induction in a variety of cell lines, a finding that was confirmed using mTOR siRNA., TOR multimerization is a conserved mechanism for TOR functioning, Results suggest that lysosomal turnover of GABARAP-PL is activated during the differentiation of C2C12 cells to myotubes without inactivation of the mTor kinase-signaling pathway., Activation of mammalian target of rapamycin is associated with postmenopausal ovarian endometriosis, Mammalian target of rapamycin (mTOR) inhibitor rapamycin enhances the sensitivity of PTEN-deficient tumor cells to the EGFR kinase inhibitor erlotinib, mTOR kinase hyperactivation is a molecular mechanism underlying the development of cytomegalic neurons, These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and in lesions associated with tuberous sclerosis., We demonstrate, for the first time in human skeletal muscle, that the regulation of Akt and its downstream signalling pathways GSK-3beta, mTOR and Foxo1 are associated with both the skeletal muscle hypertrophy and atrophy processes., activity assays in Hela cells suggested that,in phase G2 and M, the activity of mTOR was maintained at a higher level than in any other phase, eIF3i overexpression fosters the integration of growth signals by mTOR into the mRNA translation process, promoting protein synthesis and tumor growth., levels of mTOR in lymphocytes could follow the cognitive decline in Alzheimer's disease, It would seem that this increase in VEGFR-3 occurred via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002 or rapamycin were responsible for a decrease of VEGFR-3, Results reveal that the SIN1-rictor-mTOR function in Akt-Ser473 phosphorylation is required for TORC2 function in cell survival but is dispensable for TORC1 function., Phosphorylated-mTOR levels and mTOR activity were dramatically increased in HEK 293 cells with RIalpha levels reduced by siRNA., In multiple myeloma cells mTOR inhibition results a more complete abrogation of VEGF translation, and ultimately, angiogenesis., The TSC/Rheb/mTOR pathway plays a critical role in the regulation of E(2)-induced proliferation., Results suggest that FLCN, mutated in Birt-Hogg-Dube syndrome, and its interacting partner FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways., S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt, data demonstrate the ubiquitous activation of the mTOR signaling pathway in post-transplant lymphoproliferative disorder, mTOR is regulatd by polycystin-1 in polycystic kidney disease [review], Bcl-3 is required for condensation of fibrin by activated platelets, demonstrating functional significance for mTOR-regulated synthesis of the protein, mTOR-dependent pathways have roles in IFN signaling and 4E-BP1 and TSC1-TSC2 are key components in the generation of IFN-dependent biological responses, These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL., inhibition of mTOR by 5'-AMP-activated protein kinase is circumvented, model whereby nutrients signal to mTOR via activation of MAP4K3., IGFBP-2 is regulated predominantly through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway, mTOR pathway is active in 40% of patients with hepatocellular carcinomas undergoing orthotopic liver transplantation, ASCT2 silencing inhibits mTORC1 (mTOR/raptor)signaling and leads to growth repression, followed by enhanced survival signaling via mTORC2 (mTOR/rictor)and apoptosis of hepatoma cells., Rapamycin stimulates insulin-mediated glucose uptake in men under conditions known to activate the mTOR pathway., A bout of aerobic exercise restores the anabolic response of muscle proteins to insulin by improving endothelial function and Akt/mTOR signaling in older subjects., Withdrawal of Notch signals prevented stimulation of the mTOR pathway by mitogenic factors. These findings collectively suggest that the mTOR pathway is positively regulated by Notch in T-ALL cells, Changes in tissue pressure during inflammation may regulate macrophage phagocytosis by activation of PI-3K, which activates Akt2, mTOR, and p70S6K., one rational approach for mTOR-targeted lung cancer therapy is to use an mTOR inhibitor in combination with a drug that blocks PI3K/Akt activation such as a PI3K inhibitor, as we demonstrated in our study.21, It was demonstrated that immunoprecipitation of Protor-1 or Protor-2 results in the co-immunoprecipitation of other mTORC2 subunits, but not Raptor, a specific component of mTORC1., mTOR functions as a placental nutrient sensor, matching fetal growth with maternal nutrient availability by regulating placental nutrient transport. Provide a mechanism for the changes in placental leucine transport in intrauterine growth retardation., Rheb signaling to mTOR in vivo requires a Rheb switch 2-dependent interaction with an element other than the three known polypeptide components of TOR complex 1, the PI3K/AKT/mTOR signaling pathway is involved in regulation of SphK1, with AKT2 playing a key role in PDGF-induced SphK1 expression, vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors, mTOR is inactivated during hypoxia., analysis of the mammalian target of rapamycin signaling pathway in cancer [review], mTOR regulates the phosphorylation and activation of Akt in endothelial cells and a major effect of mTOR inhibition in endothelial cells is to suppress Akt-inducible pro-survival signals, used 401 to test the cellular effect of mTOR inhibition without the complicating side effects on PI3K, These results strongly suggest that the G1 arrest and the decrease in translation induced by eRF3a depletion are due to the inhibition of mTOR activity and hence that eRF3a belongs to the regulatory pathway of mTOR activity., P-Rex1 links mTOR signaling to Rac activation and cell migration, ULK1 knockdown inhibited rapamycin-induced autophagy consistent with a role downstream of mTOR, PRAS40 acts downstream of mTORC1 but upstream of its effectors, such as S6K1 and 4E-BP1, IKK alpha controls mTOR kinase activity in Akt-active, PTEN-null prostate cancer cells, with less involvement by IKK beta, AKT amplification and the mTOR/p70S6K1 pathway play an important role in human lung cancer cells acquiring CDDP resistance, the major mechanism of HER2-mediated induction of FASN and ACCalpha in the breast cancer cells used in this study is translational regulation primarily through the mTOR signaling pathway., This study identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a new regulator of iron-transferrin uptake, Proarteriosclerotic effects of interferon gamma are associated with mammalian target of rapamycin raptor complex (mTORC1) and PI-3 kinase activiation., peptidoglycan make it coincidental the release of arachidonic acid with a rapid induction of cyclooxygenase-2 protein regulated by a signaling cascade involving phosphatidylinositol 3-kinase, mTOR, and the translation machinery, Dysregulation of the tuberous sclerosis 1/mTOR signaling pathway significantly contributes to inflammation-mediated cancer pathogenesis., Finally, using dual-cistronic luciferase constructs we demonstrate that apoB 5' UTR may have weak internal ribosomal entry (IRES) translation which is not affected by insulin stimulation, and may function to stimulate basal levels of apoB translation., Overexpression of Akt1 upregulates glycogen synthase activity and phosphorylation of mTOR in IRS-1 knockdown HepG2 cells.(, mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism., PLD1 and phospho-mTOR are coexpressed in a subset of phospho-Akt-negative breast carcinomas., Introduction of mTOR inhibitors to the immunosuppressant regimen in heart transplntation may delay renal functional deterioration caused by calcineurin inhibitors., In breast cancer stem-like cells, the STAT3 pathway was found to be positively regulated by mTOR signaling, whereas PTEN served as a negative regulator of both STAT3 and mTOR signaling., These data implicate activation of mTOR in the pathogenesis of melanoma, and suggest that Rheb and mTOR may be targets for melanoma therapy., Bnip3, a hypoxia-inducible Bcl-2 homology 3 domain-containing protein, directly binds Rheb and inhibits the mTOR pathway., Inhibition of mTOR was the idea behind the development of new targeted agents in advanced renal cell carcinoma (Review)., IFNalpha-induced apoptosis requires activation of ERK1/2, PKCdelta, and JNK downstream of PI3K and mTOR, and it can occur in a nucleus-independent manner, thus demonstrating that IFNalpha induces apoptosis in the absence of de novo transcription., This is the first study showing mTOR pathway dysregulation and an increased expression of proapoptotic Bax protein in cardiac rhabdomyomas associated with tuberous sclerosis complex., findings suggest that FKBP38 is an endogenous inhibitor of mTOR, whose inhibitory activity is antagonized by Rheb in response to growth factor stimulation and nutrient availability, The PKB-dependent mechanism of insulin-stimulated c-Myc expression in HT29 cells was shown to involve the activation of mTOR in c-Myc translation, analysis of coupled down-regulation of mTOR and telomerase activity during fluorouracil-induced apoptosis of hepatocarcinoma ce, metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, a key regulatory role of the Akt/mTOR pathway in the generation of the effects of As(2)O(3), mTOR signaling pathway is playing a role in the greater synthesis of muscle proteins when resistance exercise is followed by essential amino acids and carbohydrate ingestion, activation of mTORC1 signalling by phorbol esters does not require PRAS40 to be phosphorylated at Thr(246), bind to 14-3-3 or be released from mTORC1., the activities of AMP-activated protein kinase, protein kinase B, and mammalian target of rapamycin by limiting energy availability with 2-deoxyglucose, The mTOR pathway plays a critical role in histocompatibility antigen HLA class I antibody-induced cell proliferation and cell survival., Alexander disease mutant GFAP accumulation stimulates autophagy, in a manner regulated by p38 MAPK and mTOR signaling pathways., hamartomatous TSC skin tumors are induced by paracrine factors released by two-hit cells in the dermis, and proliferation with mTOR activation of the overlying epidermis is an effect of epiregulin, importance of mTOR in CCL5-mediated T-cell mig, Akt and mTOR activation have distinct functional relevance in mantle cell lymphoma, The results demonstrate that multiple muscarinic receptor subtypes regulate mTOR, and that both MAPK-dependent and -independent mechanisms may mediate the response in a cell context-specific manner., Active AKT and mTOR, were present in all adenomas, carcinomas, and in normal colorectal mucosa., after mTORC1 kinase activation by upstream regulators, PRAS40 is phosphorylated directly by mTOR, thus contributing to the relief of PRAS40-mediated substrate competition., The PI3K/Akt/mTOR signaling pathway is implicated in the development of cervical cancer., CCI-779 inhibits mTOR signaling through an FKBP12-independent mechanism that leads to profound translational repression in cancer cells., SKAR-mediated recruitment of activated S6K1 to newly processed mRNPs serves as a conduit between mTOR checkpoint signaling and the pioneer round of translation when cells exist in conditions supportive of protein synthesis., Inhibition of protein kinase mTOR, a key nutrient sensor impairs cell proliferation., Cav-1 increases the basal and TGF-beta1-induced expression of type I procollagen by regulating two opposite signaling pathways, deregulated PKB/AKT stabilizes Mcl-1 expression in a mammalian target of rapamycin (mTOR)-dependent pathway, Focal brain malformations, Inhibition of mTOR may provide a nontoxic adjunct to therapy directed against malignant mesothelioma, especially in those with high baseline expression of p-S6K, We show here that mTOR downstream from Akt controls NF-kappaB activity in PTEN-null/inactive prostate cancer cells via interaction with and stimulation of IKK., interaction of PI3K/Akt/mTOR and p53 pathways after their simultaneous blockade using the dual PI3K/mTOR inhibitor PI-103 and the Mdm2 inhibitor Nutlin-3., mTOR signaling pathway is activated in two endometrial carcinoma cell strains and the status of activation is related with PTEN expression of the cells, SGK1 is an mTOR-raptor substrate and mTOR may promote G1 progression in part through SGK1 activation and deregulate the cell cycle in cancer., IL-4 activates mTOR signaling in T-ALL cells, which is critical for cell cycle progression of T-ALL cells, Studies suggest that TF-FVIIa-FXa-mediated signaling modulates mTOR pathway activation, which regulates in part breast cancer cell migration., mTOR inhibition could enhance the effects of 5-aza-dC on suppressing cell proliferation and arresting cell cycle in human gastric cancer cell lines, ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo, mTOR inhibition by rapamycin alters gene expression in two breast cancer cell lines., FKBP38 is a bona fide effector of Rheb and the ability to interact with FKBP38 is important for Rheb as an activator of mTOR, Study identified a new link between mTOR, p73, and p73-regulated genes associated with autophagy and metabolic pathways., phosphatases and pRB have important roles in IGF-I/mTOR-mediated cell survival, in prostate cancer cells at least two mechanisms of drug resistance are interconnected. PTEN and mTOR signaling were shown, BCR-ABL leukemogenesis inis blocked by PI3K in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells, The state of activation of components of mTOR, Ras/Raf kinase/ERK, and nuclear factor (NF)-kappaB signal transduction pathways, as well as cell cycle protein analyte correlates in gastric adenocarcinoma cases, was examined., MAPK activation is a consequence of mTORC1 inhibition in neoplasms, stromal cell-derived factor-1 and transforming growth factor-beta control the quiescence/cycling switch of CD34(+) progenitors through FoxO3 and mammalian target of rapamycin, Combining MTOR inhibition with metronomic chemotherapy in targeting angiogenesis is reported., Inhibition of PI3-K/Akt induces a 40% decrease of cyclin D1 half-life as a result of accumulation of the dephosphorylated/active form of GSK-3beta within the nucleus, where it can phosphorylate cyclin D1 on Thr286 thereby promoting its nuclear export., there are two parallel cell-survival pathways in prostate cancer cells, findings show mTOR is targeted for ubiquitination & degradation by binding to FBXW7; breast cancer cell lines & primary tumors showed a reciprocal relation between loss of FBXW7 & deletion or mutation of PTEN, which also activates mTOR, Target of Rapamycin 1 causes neurons to have multiple axons and the translation of SAD kinase increases as well, This study suggests a pivotal role of PI3 K, MAPK and mTOR pathways, via tuberin, in post-transcriptional control of CXCR4., activation of the Akt-mTOR-p70S6K pathway plays a significant role in HCC progression by promoting neoangiogenesis., mTOR inhibition enhances chemosensitivity in hepatocellular carcinoma, The mTOR activated pS6K(ser240 / 244) was detected in in 86.7% of ameloblastomas., TORC2 inhibition reduced proliferation and anchorage-independent growth of breast cancer and prostate cancer cell lines., Inhibition of PI3K or mTOR reduced the level of Rap1B, which acts downstream of Rheb and mTOR. The ubiquitin E3 ligase Smurf2 mediates the restriction of Rap1B by initiating its degradation., These data identify the TSC2-mTOR pathway as a key regulator of innate immune homeostasis with broad clinical implications for infectious and autoimmune diseases, vaccination, cancer, and transplantation., mTOR is a indispensable component of PRR signal pathways, which orchestrates the defense program of innate immune cells., Dysregulation of the TSC-mTOR pathway may cause not only tumor development but also metabolic disorders such as diabetes and its comp, MTOR signaling has a critical role in the pathogenesis of HCC, with evidence for the role of RICTOR in hepato-oncogenesis., expression of hypoxia-inducible factors 1 alpha and 2 alpha is dependent on mTORC1 and mTORC2, RalGDS and RalA act downstream of Rheb and that RalA activation is a crucial step in nutrient-induced mTORC1 activation, results suggest a novel mechanism by which AMPK activation after hypoxia-induced energy stress may be crucial in regulating REDD1 expression to control the mTOR pathway in head and neck squamous cell carcinoma, Analysis of likelihood of concordance between the mTOR pathway interactome and mTOR genes being linked to human lupus find the mTOR pathway implicated as a critical contributor to human lupus., the expression of VE-cadherin is dependent on mTOR and PI3K signaling., mTORC2 and Akt facilitate CD40-inducible expression of VEGF in endothelial cells, In podocytes, the expression level of the slit-diaphragm proteins nephrin and transient receptor potential cation channel 6 as well as the cytoskeletal adaptor protein Nck are regulated by mTOR., mTOR and eIF4E have a role in preventing progression of ovarian cancer, FAK, mTOR and IGF-IR are inhibited by TAE226 in esophageal cancer cells, Melatonin attenuates methamphetamine-induced deactivation of the mammalian target of rapamycin signaling to induce autophagy in SK-N-SH cells, an important role of PKC-delta and PI3K/Akt1,2 pathways in activating mTOR as an endogenous modulator to ensure a tight regulation of NF-kappaB signaling of ICAM-1 expression in endothelial cells., inhibition of the PI3K-AKT-mTOR pathway potently increases sensitivity of melanoma cells to chemotherapy, mTOR may function not only in the proliferation of tumor cells as an effector molecule downstream of EGFR but also possibly in the morphogenesis of AC., Akt/mTOR-dependent translation of HIF-1alpha plays a critical role in the postirradiation up-regulation of intratumoral HIF-1 activity in response to radiation-induced alterations of glucose and oxygen availability in a solid tumor., Expression of mTOR and 4EBP1 characterize high-grade, high-stage endometrial adenocarcinomas and might be predictive markers of a response to rapamycin., KAI1/CD82 decreased the metastatic phenotype of H1299 lung carcinoma cells by down-regulating Rac1 expression through the PI3K/Akt/mTOR pathway., Resveratrol inhibits the mTOR mitogenic signaling evoked by oxidized LDL in smooth muscle cells, After treatment with everolimus, expression of p-mTOR, HIF-1alpha and VEGF was shown to be sharply depressed in clear cell adenocarcinoma, S2448 phosphorylated mTOR binds to both raptor and rictor., Insulin promotes the interaction of Hsp90 with the IP(3)R to dampen its Ca(2+) release activity by a complex mechanism involving mammalian target of rapamycin and the Src kinase., mTOR inhibition radiosensitizes soft tissue sarcoma and tumor vasculature, PTEN, PTEN/p-AKT and PTEN/p-mTOR have roles in extrahepatic cholangiocarcinoma, This review presents research highlighting the specificity of mechanical signaling of mTOR in mammalian skeletal muscle, and the negative regulation of mTOR signaling., mTOR upregulation in healthy portions of TS patients' skin provides an explanation to such a variety of lesions observed in this neurocutaneous condition, genetic variations in FRAP1 were associated with survival inesophageal cancer, Phosphorylation of AKT and mTOR is correlated with anaplastic lymphoma kinase expression in anaplastic large cell lymphoma., EGFR signals to mTOR through PKC and independently of Akt in glioma, Phosphorylated AKT as well as activated mTOR and its down-stream effector S6K were strongly expressed in cystic epithelia of autosomal recessive polycystic kidney disease., activation of mTOR causes the loss of TCRzeta in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation, Study shows show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids is the rate-limiting step that activates mTOR., Overproduction of cyclin D1 is dependent on activated mTORC1 signal in nasopharyngeal carcinoma, mTORC1 suppresses autophagy through direct regulation of the approximately 3-MDa ULK1-Atg13-FIP200 complex., FKBP38 is not the long-sought Rheb effector linking Rheb to mTORC1 activation., Overexpression of phosphorylated mammalian target of rapamycin is associated with lymph node metastasis in gastric cancer., Localisation of p-mTOR may play an important role in tumour progression and outcomes in patients with gastric cancer., The ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling., p53 activation may downregulate the AKT/mTOR pathway through a mechanism involving AMP kinase in mantle cell lymphoma, Folliculin regulates the activity of TORC1, and a new paradigm in which both inappropriately high and inappropriately low levels of TORC1 activity can be associated with renal tumorigenesis., VEGF-A signalling acts on tumour cells as a stimulator of the AKT/mTOR pathway., TORC-specific phosphorylation of mammalian target of rapamycin (mTOR), ATG13 and ULK1 are phosphorylated by the mTOR pathway in a nutrient starvation-regulated manner, indicating that the ULK1.ATG13.FIP200 complex acts as a node for integrating incoming autophagy signals into autophagosome biogenesis., These results reveal for the first time that PP-mTOR(Ser2481) may be unexpectedly involved in the terminal stages of cytokinesis., The ethanol-mediated repression of mTOR signaling coupled with decreased in vivo lymphoma growth underscore the critical role of mTOR signaling and translation in lymphoma., Resistance exercise rapidly increases mTOR signaling and may decrease myostatin protein expression in muscle; whey protein increases and prolongs the mTOR signaling response., Expression of mTOR pathway components is related to the invasive capacity of hepatocellular carcinoma cells and may be used as a prognostic indicator in hepatocellular carcinoma., Activation of PI3K via APRIL results in phosphorylation of Akt and mTOR in a TACI-dependent manner, mediating follicular lymphoma B-cell proliferation, mTOR signaling is one major mechanism in a tightly regulated network of intracellular signal pathways including the JAK/STAT system to regulate invasion in human trophoblast cells by secretion of enzymes that remodel the extra-cellular matrix., mTORC1 and mTORC2 complexes have distinct, non-redundant functions in MO7e MK cell proliferation, and development, Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size., Components of the Pi3K-mTOR signaling pathway were observed in a higher percentage of neuronal cells in gangliogliomas compared with control cortex, Results show that blocking the PI-3K/Akt/mTOR signalling pathway might be a compelling target for the therapy of ATL., This study describes the small molecule Ku-0063794, which inhibits both mTORC1 and mTORC2, but does not suppress the activity of 76 other protein kinases or seven lipid kinases., mTOR activation as important requirements for naive CD4 T cell proliferation, mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells, Study identifies DEPTOR, a novel mTOR-interacting protein whose deregulated overexpression in multiple myeloma cells represents a mechanism for activating PI3K/Akt signaling and promoting cell survival, A model where IQGAP1 serves as a phosphorylation-sensitive conformation switch to regulate the coupling of cell growth and division through a novel CDC42-mTOR pathway., Data provide the first evidence that site-specific mTOR phosphorylation regulates mTORC1 function., Activation of the AKT/mTOR signaling pathway plays an important role in the development of diffuse large B-cell lymphoma, and is closely related to the low or non-expression of bcl-6., mTORC1-mediated consequences on cell cycle and cell size are separable and do not involve effects on mTORC2 activity., mTOR expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung adenocarcinoma patients as well as incorporation of mTOR into clinical decisions., mammalian target of rapamycin activity is essential for expansion of CD34(+) hematopoietic progenitor cells during myelopoiesis, Studies indicate that dampening the TOR pathway leads to widespread protection from an array of age-related diseases., a new role for mTOR and alpha4/PP2Ac in the control of STAT1 nuclear content, and the expression of interferon-gamma-sensitive genes involved in immunity and apoptosis., Studies indicate inhibition of the PI3K/AKT/mTOR pathway is not only a potential first-line therapeutic strategy in ovarian cancer but also could be used in recurrent disease as a means of reversing acquired chemotherapy resistance., GOLPH3 regulates cell size, enhances growth-factor-induced mTOR (also known as FRAP1) signalling in human cancer cells, and alters the response to an mTOR inhibitor in vivo, Data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold-dependent., commitment of cell transformation by Aurora-A is determined by at least co-activation of Akt/mTOR pathway, It was concluded that the mTOR pathway represents an important intracellular regulatory link between nutrient and growth factor concentrations and amino acid transport in the human placenta., the activation of the mammalian target of rapamycin (mTORC)1 pathway in 29 cases of AIDS-related lymphoma was identified., Results show interaction between CCR7 and its ligand CCL19 induces phosphorylation of mTOR and its target p70s6k. This phosphorylation is abolished by inhibition of CCR7 and PI3K/Akt, indicating that mTOR is involved in the CCR7-PI3K cascade., Results suggest that ribavirin enhances activities of mTOR and p53, which may account for its antiviral and antitumor effects., GOLPH3 links the Golgi network to mTOR signaling and human cancer, Report EGFR-dependent and independent activation of Akt/mTOR/p70S6 kinase/4E-BP1 cascade in bone and soft tissue tumors., 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., there is a high expression rate of mTOR poorly differentiated neuroendocrine carcinomas (large-cell type), Studies indicate that drugs are effective in targeting essential molecular pathways of BRAF, PTEN, Akt and mammalian target of rapamycin., Studies elucidated the inhibitory mechanism in which mTORC1 phosphorylates the autophagy regulatory complex containing unc-51-like kinase 1 (ULK1), the mammalian Atg13 protein, and focal adhesion kinase interacting protein of 200 kD (FIP200)., Report expression and mechanism of mammalian target of rapamycin in age-related renal cell senescence and organ aging., Report involvement of mTORC1 and mTORC2 in regulation of glioblastoma multiforme growth and motility., EPAC-mediated cellular effects require activation of the B-Raf/ERK and mTOR signaling cascades, TOR beta has the potential to regulate the the cell cycle and to stimulate cell proliferation., Phosphorylated mTOR expression was associated with metastatic lymph nodes in pT2b gastric cancer., Studies indicate that mTOR inhibition treatment strategy was owing to the characteristic overexpression of cyclin D1 regulated by mTOR signaling., mTORC1 signaling is inhibited by perhexiline, niclosamide, amiodarone, and rottlerin, we discuss clinical consequences of mTOR-inhibitor therapy & aim to integrate this recent data into our current view of molecular mechanisms of clinically employed mTOR inhibitors & discuss their relevance with special emphasis to transplantation[review], The expression of mTOR is infrequent and is associated with COX-2 overexpression., mTOR is inhibited by Timosaponin AIII in a process that involves induction of endoplasmic reticulum stress, mTOR regulates muscle regeneration through kinase-independent and kinase-dependent mechanisms at the stages of nascent myofiber formation and myofiber growth, respectively., mTOR/Akt2 is required for optimal PPARgamma activation. Patients who receive SESs during concomitant RSG treatment may be at risk for delayed stent healing., Data show that everolimus/RAD001 significantly inhibits cell viability in a dose- and time-dependent fashion, and diminishes phosphorylation of Akt downstream targets, mTOR and p70S6K, in human medullary thyroid carcinoma cells., Data inidicate that FTS could be a promising treatment for Rheb- and mTOR-dependent cancers., Complex raptor phosphorylation functions as a biochemical rheostat that modulates mTORC1 signaling in accordance with environmental cues., germ line genetic variations in the PI3K-AKT-mTOR pathway may have roles as bladder cancer susceptibility factors, We provide evidence for a previously unrecognized phospholipase C-gamma1 (PLC-gamma1)-controlled mechanism of mTOR/p70S6-kinase activation, Oscillatory shear stress induces osteoblast-like cell proliferation through activation of alpha(v)beta(3) and beta(1) integrins and synergistic interactions of FAK and Shc with PI3K, leading to the modulation of ERK and Akt/mTOR/p70S6K pathways., The key signaling molecules in the PI3K signaling cascade, the abnormalities known to occur in thyroid cancer, and the potential for therapeutic targeting of PI3K pathway members are discussed., The results reveal an opposing and uncoupling effect of mTOR and S6K1 in regulating TF expression., mTOR pathway is essential for embryoid body formation of amniotic fluid stem cells., These results indicate that forskolin (FSK) does not activate the Akt-mTOR pathway in human skeletal muscle; however, these results suggest that FSK may inhibit the actions of insulin on this pathway., High MTOR is associated with osteosarcoma progression., mTOR has a role in bladder cancer [commentary], The mTOR/S6 signal pathway is activated in refractory/relapsed aplastic anemia, and can be suppressed by rapamycin or CTLA-4Ig., These findings reveal a novel functional link between mTOR and DNA damage responses pathways in the nucleus potentially operating as a survival mechanism against unfavorable growth conditions., Studies review the oncogenes and tumor suppressors comprising the regulatory network upstream of mTOR, highlight the cancers in which mTOR is activated., Serine 2481-autophosphorylation of mammalian target of rapamycin (mTOR) couples with chromosome condensation and segregation during mitosis, elevated levels of activated p-mTOR in renal cell carcinoma result predominantly from an increased mTOR phosphorylation rather than from protein overexpression, RT-PCR studies revealed that MTOR, eIF4E binding protein and ribosomal protein S6 kinase are expressed at mRNA level in both JEG-3 and BeWo human placental choriocarcinoma cell lines., Data show a novel mechanism for the sensitization to DR-induced apoptosis linking glucose metabolism to Mcl-1 downexpression, and provide a rationale for the combined use of DR ligands with AMPK activators or mTOR inhibitors in the treatment of cancers., Dissecting the role of mTOR, Results are consistent with the hypothesis that ERK and mTOR signaling interact at multiple levels to regulate tumor growth in vivo, and support the testing of MEK plus mTOR inhibitor combinations in pancreatic cancer patients., findings suggest that CCL2 hyperactivates mTORC1 through simultaneous regulation of both AMPK and Akt pathways and reveals a new network that promotes prostate cancer, mTORC1- and likely mTORC2-associated mTOR Ser-2481 autophosphorylation directly monitors intrinsic mTORC-specific catalytic activity and reveal that rapamycin inhibits mTORC1 signaling in vivo by reducing mTORC1 catalytic activity, Studies indicate that the PI3K/Akt/mTOR pathway plays a critical role in breast cancer development and resistance to traditional anti-tumor strategy., mTOR is closely involved in gene regulation at the promoters, which is a conserved mechanism to control RNA polymerase I- and III-dependent genes that are critical for protein synthesis and cell growth., Inhibition of mTORC1, pathologically activated by loss of the TSC1/TSC2 tumor suppressor complex, by sirolimus is a rational mechanistic target for therapy in PEComas., integrity of late endosomes is essential for amino acid- and insulin-stimulated mTORC1 signaling and blocking the early/late endosomal conversion prevents mTOR from interacting with Rheb in the late endosomal compartment, mammalian target of rapamycin has a role in bladder cancer, and its inhibition could be a therapeutic strategy, Data show that the contraction-induced increase in early post-exercise mTOR signalling and muscle protein synthesis is independent of sex and appears to not play a role in the sexual dimorphism of leg skeletal muscle in young men and women., Bcl-xl, but not VDAC1, is a kinase substrate for mTOR in vitro, and mTOR regulates the association of Bcl-xl with mTOR., in clear cell ovarian cancer cells, overexpression of mir-100 inhibited mTOR signaling & enhanced sensitivity to RAD001; experiments revealed strong candidate miRNAs & their target genes that may contribute to pathogenesis of clear cell ovarian cancer, Overexpression of the mammalian target of rapamycin is associated with non-small cell lung cancer., mTOR has a role in regulation in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex, The mTOR signaling pathway in K562/DNR cells is activated by arsenic trioxide., ARD1 functions as an inhibitor of the mTOR pathway and that dysregulation of the ARD1-TSC2-mTOR axis may contribute to cancer development, Low-intensity resistance exercise in combination with blood flow reduction enhances mTORC1 signaling and muscle protein synthesis in older men., AKT, mTOR, and DJ-1 in primary and metastatic OC and present data linking these proteins with aggressive clinical behavior in the cancer., The activation of the PI-3K/mTOR/translational pathway is important for IFNgamma-mediated VEGF expression in retinal pigmented epithelial cells., results identify a cytoplasmic pathway for ROS-induced ATM activation of TSC2 to regulate mTORC1 signaling and autophagy, identifying an integration node for the cellular damage response, Data indicate that compound 26 (PKI-587) has shown excellent activity as highly efficacious PI3K/mTOR inhibitor., Structure/function analyses have led us to identify two segments in REDD1 that are essential for mTORC1 inhibition., Observations suggest that mTOR is likely to be involved in sensing membrane sterol concentrations in endothelial cells., coordinated regulation of IGF-1/AKT/mTOR pathways and the endosomal compartment by the p53 pathway integrates the molecular, cellular, and systemic levels of activities in response to stress [review], Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer., cisplatin-triggered activation of AMPK and subsequent suppression of mTOR activity can induce an autophagic response that protects tumour cells from cisplatin-mediated apoptotic death, RAD001 can inhibit mTOR signaling and proliferation in SEG-1 esophageal cancer cells in vitro., Studies indicate that mammalian target of rapamycin (mTOR) pathway has a critical role in oncogenesis has made it a potential therapeutic target., The inhibition of mTORC2 reduces colon cancer cell proliferation in vitro and tumor xenograft formation in vivo., Amino acid sufficiency phosphorylates MAP4K3/Ser170, activating mTORC1, but amino acid restriction causes MAP4K3 to interact with PP2A(T61 epsilon), promoting dephosphorylation of Ser170, MAP4K3 inhibition, and, inhibition of mTORC1 signaling., Hypoxia enhances BMP-2 expression in osteoblasts by an HIF-1alpha-dependent mechanism involving the activation of ILK/Akt and mTOR pathways., High glucose stimulated mesenchymal stem cell proliferation through cyclin D1/E and TGF-beta(1) expression via Ca(2+)/PKC/MAPKs as well as PI3K/Akt/mTOR signal pathways., mTOR inhibition led to an increase in the occupancy of Maf1 on a set of Pol III-dependent genes, with concomitant reduction in the binding of Pol III and Brf1, findings provide the first linkage of host signals to parasite-mediated host cell reorganization and demonstrate migratory suppression as a novel functional consequence of this process that is associated with mTORC2-mediated centrosome constraint, Curcumin significantly inhibited NF-kappaB and attenuated the effect of irradiation-induced prosurvival signaling through the PI3K/Akt/mTOR and NF-kappaB pathways in these gut-specific endothelial cells., heterogeneous ribonucleoprotein F is involved in the regulation of cell proliferation via the mammalian target of rapamycin/S6 kinase 2 pathway, GSK-3 activity in DC is regulated via signaling linked to mTOR and modulates their capacity both to produce IL-12p40/p70 and induce forkhead box p3 in CD4(+) T cells under inflammatory conditions., These results suggest that the mTOR signaling pathway is regulated by LMP1 expression in nasopharyngeal carcinoma., mTOR, specifically mTORC2, is the hydrophobic motif kinase for SGK1 and is required for ENaC-mediated Na+ transport., SGK1 interacted selectively with rictor but not with raptor, suggesting selective recruitment of SGK1 to mTORC2., Phosphorylated mTOR expression is associated with esophageal squamous cell carcinoma., 28 single nucleotide polymorphisms located in six genes of mTOR pathway were significantly associated with the risk of bladder cancer, sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner, EphA2 mutation in lung squamous cell carcinoma promotes increased cell survival, cell invasion, focal adhesions, and mammalian target of rapamycin activation, Data identify DEAF1 as an interactor and in vitro substrate of GSK3A and GSK3B that interacts with the phosphatidylinositol 3-kinase-mammalian target of rapamycin pathway., Notch-1 can positively regulate Akt-mTOR pathways, which are associated with glioma cell proliferation and apoptosis., SOCS3 suppresses hepatitis C virus replication in an mTOR-dependent manner., Findings illustrate a mechanism for the cardioprotective effects of lovastatin through inhibition of Rheb and mTORC1 and promotion of a differentiated vascular smooth muscle cell phenotype., Rag-Ragulator-mediated translocation of mTORC1 to lysosomal membranes is the key event in amino acid signaling to mTORC1, Examined insulin signaling in adipocytes from T2D patients, and contrary to findings in animal studies, we observed attenuation of insulin activation of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1)., RHEB is an MTOR activator that facilitates multistage carcinogenesis through induction of multiple oncogenic mechanisms, These findings indicate that mTOR pathway activation frequently occurs in urothelial carcinoma (UCC) and that mTOR inhibition may be a potential means to reduce UCC growth., IL-8 reverses an mTOR/S6K-led down-regulation of PLD2 expression and enables PLD2 to fully function as a facilitator for cell migration, FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor, isoaspartate formation repair modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain, aberrant nuclear accumulation of LKB1 caused by STRADalpha deficiency contributes to hyperactivation of mTORC1 signaling and disruption of neuronal lamination during corticogenesis, Data show that that knockdown of either Tti1 or Tel2 causes disassembly of mTORC1 and mTORC2., Rather than acting directly by binding to mTORC1, the lipid second messenger phosphatidic acid, together with leucine, promotes mTORC1 signaling through enhancement of parallel pathways upstream of the mitogen-activated protein kinase activity of mTORC1., This study reveals that mTORC2 is a critical target of PLD-mediated survival signals and identifies SGK1 as a downstream target of mTORC2 for the stabilization of HDM2., These data suggest that the raptor/mTORC1 pathway may play a role in increased IRES-dependent mRNA translation during mitosis and in rapamycin insensitivity., Data demonstrate a key role of Rab and Arf family small GTPases and intracellular trafficking in mTORC1 activation., blocking of OPN-induced ICAM-1 expression through mTOR/p70S6 kinase signaling pathway may be an important therapeutic strategy for the treatment of breast cancer., mTOR inhibition with sirolimus can improve recurrence-free survival, while simultaneously providing adequate immunosuppression, patients with hepatocellular carcinoma that receive a liver transplant., mTOR was strongly expressed in renal cyst-lining cells and bile ducts from autosomal-recessive polycystic kidney disease, PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer., The majority of ER-positive breast tumours treated with everolimus showed a significant reduction in genes involved with proliferation, these may serve as markers of response and predict which patients will derive most benefit from mTOR inhibition., PI3K-PKB-mTOR signaling plays a crucial role in the development of functional CD34-derived myeloid Dendritic cells, Findings not only reveal the crucial role of mTOR in physiology and pathology, but also reflect the complexity of the mTOR signaling network., The role of the ezrin-mTOR pathway on the invasive properties of fibroblast-like synoviocytes, was examined., results are consistent with a "Gas and Brake" model in which mTOR inhibition also controls a buffering mechanism that counterbalances the autophagic flux and prevents its overactivation under nutrient deprivation, Data show that mTORC1 is an obligate dimer with an overall rhomboid shape and a central cavity., Contribution of human amniotic fluid stem cells to renal formation depends on mTOR., Maf1, a repressor that binds and inhibits pol III, is phosphorylated in a mTOR-dependent manner both in vitro and in vivo at serine 75, a site that contributes to its function as a transcriptional inhibitor., status of the mTOR pathway can determine, at least in part, the choice between senescence and quiescence in p53-arrested cells., Phospho-mTOR evaluation might be of clinical utility as a potential marker for identification of steatosis, non-alcoholic steatohepatitis-related cirrhosis in cases mistakenly considered as cryptogenic cirrhosis owing to paucity of clinical data., Expression of constitutively active mTOR conferred resistance to cryptotanshinone inhibition of cyclin D1 expression and Rb phosphorylation, as well as cell growth., Down-regulation of mTOR is associated with advanced pancreatic cancer., Co-localization of dysfunctional adhesion molecule on glia (AMOG) with precursor cell marker CD34 and phosphorylated S6, a marker of mTOR activation, may contribute to neuronal hyperexcitability., The LKB1/AMPK/TSC tumor suppressor axis is functional in acute myeloid leukemia., Data suggest that the absent or decreased expression of PTEN and the actived mTOR may play important roles in carcinogenesis and metastasis of NSCLC., Elevated expression of phosphorylated S6 in Xp11 translocation renal cell carcinomas suggests the mTOR pathway as an attractive potential therapeutic target for these neoplasms., VEGF stimulation results in mTOR signaling activation which changes the phosphorylation status of 4E-BP1, the downstream of mTOR signaling, and ultimately contributes to the translation initiation of Livin protein, We show for the first time an association between pmTOR and better survival in patients with endometrial cancer., The phosphorylation of inositol 1,4,5-trisphosphate receptors by mTOR protein appears to be a general mechanism to potentiate Ca2+ release in growing cells., elevated PLD-mTOR signaling, which is common in human cancer cells, is critical for the metabolic shift to aerobic glycolysis., mTOR exerts divergent immunoregulatory functions during dendritic cell activation and differentiation, In patients with metabolic syndrome X, we found a reduction of mTOR and other mTOR-related molecules involved in insulin resistance, cell repair, coagulation and vasculogenesis, Inhibition of the mTOR signal may be a promising strategy for radiosensitization with no relevance to p53 gene status from the aspects of lung cancer cell lethality and cell growth depression., ATCAA-10 modulates the activity of two signaling pathways, PI3K/AKT/mTOR and AMPK/mTOR, resulting in the inhibition of cancer cell growth., these data demonstrate a differential mTOR activation status in the spectrum of pulmonary neuroendocrine tumors, possibly suggesting that mTOR pathway profiling might play a predictive role in candidate patients for mTOR-targeted therapies., Data indicate that delta-tocotrienol protects mouse bone marrow and human CD34(+) cells from radiation-induced damage through extracellular signal-related kinase activation-associated mammalian target of rapamycin survival pathways., The mTOR pathway is activated in monocytes within 1 hour of lipopolysaccharide stimulation., results suggest a novel regulatory mechanism for mTORC1 in which the cAMP-determined dynamic interaction between Rheb and PDE4D provides a key, unique regulatory event, and propose a new role for PDE4 as a molecular transducer for cAMP signaling., Report good tolerability, feasibility of prolonged treatment, antitumor activity, and favorable pharmacologic profile of mTOR inhibitor ridaforolimus with capecitabine., 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., These data suggest that mTOR mitigates adverse outcomes of pressure overload and that this cardioprotective effect of mTOR is mediated by regulation of the inflammatory reaction., The CK2 phospho-dependent interaction between TEL2 and the R2TP complex affects phosphatidylinositol 3-kinase-related kinase functions and is essential for mTOR and SMG1 stability in vivo., Our data suggest that resistance exercise followed by protein feeding stimulates MPS over that induced by feeding alone in part by enhancing the phosphorylation of select proteins., Third-line sorafenib appears to be active and well tolerated in metastatis renal cell carcinoma after first-line sunitinib and second-line mTOR inhibitors., inhibiting mTOR in gastric cancer inhibits progression of the disease, Report schedule-dependent inhibition of T-cell lymphoma cells by cotreatment with the mTOR inhibitor everolimus and anticancer agents., We have shown that mTOR play an important role in the development of hepatocellular carcinoma; that mTOR inhibition induced by antisense pEGFP-C1-mTOR could inhibit cell proliferation and migration and induced apoptosis of hepatoma cell ines., Data suggest that the PI3K/Akt/mTOR pathway may contribute to maintenance of quiescence of cancer stem cells., Constitutive activation of EGFR/Akt/mTOR pathway was present in defined subset of nonsmall cell lung carcinomas., The PI3 kinase/mTOR blocker NVP-BEZ235 overrides resistance against irreversible ErbB inhibitors in breast cancer cells., Results show that oncogenic Nrf2 mutation induces dependence on the mTOR pathway during carcinogenesis., Combined inhibition of PI3K and mTOR, which activates autophagy without activating Akt, cooperated with inhibition of autophagy to cause glioma cells to undergo apoptosis., a novel regulatory mechanism by which mitogenic and oncogenic activation of the Ras/MAPK pathway promotes mTOR signaling, Although the mechanism of load-induced mTORC1 activation remains to be determined, it is clear that it does not require classical growth factor signaling., Rapamycin inhibits the growth of CNE-1 and CNE-2 cells by inhibiting the progression of cell cycle, which could be achieved through decreasing the expression of mTOR., Hypoxia results in ataxia telangiectasia mutated (ATM)-dependent phosphorylation of hypoxia-inducible factor 1-alpha (HIF-1alpha) on serine(696) and mediates downregulation of mTORC1 signaling., The results suggest that mTOR pathways can mediate the limiting effects of Gln deprivation on protein synthesis according to its severity., DDIT4, an inhibitor of mTOR signaling, is a direct target for 1,25(OH)(2)D(3) and VDRE-BP, and functions to suppress cell proliferation in response to vitamin D, kinase activity sets regulatory T cell responsiveness, mTOR shows considerable variations in expression and activity patterns in gastroenteropancreatic neuroendocrine tumors in dependence of tumour location and metastatic status., There is an increased mitochondrial dependence upon mTORC2 dependent cell growth due to PTEN loss, a compensatory feedback regulation in which the activation of Akt is inhibited by up-regulation of PHLPP through mTOR, and this mTOR-dependent expression of PHLPP subsequently determines the rapamycin sensitivity of cancer cells., concluded that LDHB is a downstream target of mTOR that is critical for oncogenic mTOR-mediated tumorigenesis, mTOR activation from plasmid vectors occurs via different pathways in PC3 and 293T cells, DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence., Tamoxifen down-regulates survivin expression in HepG2 cells and it is mediated by transcriptional and post-transcriptional level via PI3K/Akt/mTOR pathway to induce apoptosis., Differential expression of neuronal-related genes and increased mTOR activation may underlie phenotypic variations in NF1-associated low grade astrocytomas., Mammalian target of rapamycin regulated level of beta-catenin in hepatocellular carcinoma. Both mammalian target of rapamycin and beta-catenin play important roles in growth, metastasis, and prognosis of hepatocellular carcinoma., Results indicate that activation of Akt is involved in Brca1-deficiency mediated tumorigenesis and that the mTOR pathway can be used as a novel target for treatment of Brca1-deficient cancers., Oleanolic acid inhibited mTORC1 signaling and induced G1 cell cycle arrest, and inhibited mTORC2 signaling and induced apoptosis in osteosarcoma cells., Data show that under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK., mTOR plays a role in the regulation of KSHV replication and transcription activator expression and, therefore, KSHV production, In the HER2 overexpression type and triple-negative breast carcer, tumor cell proliferation and survival in the hypoxic tumor environment could possibly be due to disinhibition of the mTOR pathway and HIF-1alpha stabilization by downregulation of REDD1., p-mTOR was not associated with expression of its downstream effectors or prognostic factors in ovarian cancer., Study shows activation of mTOR signaling in primary T-ALL cells evolving in the leukemic bone marrow, and supports the inclusion of mTOR antagonists in current therapeutic regimens for this cancer., show that E2F1 is capable of inducing growth by regulating mTORC1 activity, Dependence of Evi1-expressing leukemic cells on AKT/mTOR signaling provides the first example of targeted therapeutic modalities that suppress the leukemogenic activity of Evi1., PI3K/AKT/mTOR signalling pathway activation is a common event in high-risk neuroblastoma., Leucine restriction did not result in inhibition of mTOR pathway in vitro., pattern of megakaryocytopoiesis is associated with up-regulated thrombopoietin (TPO) signaling through mammalian target of rapamycin (mTOR) and elevated levels of full-length GATA-1 and its targets, These data suggest that mTORC1 is involved in the production of all classes of human cytomegalovirus proteins., Studies define a distinct role for WIPI1 and TORC1 signaling in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy., Estimates of eIF4E activity predict sensitivity to mTOR inhibition in cell lines., results suggest that GRp58/ERp57 is involved in the assembly of mTORC1 and positively regulates mTORC1 signaling at the cytosol and the cytosolic side of the endoplasmic reticulum, Components of the mTOR/HIF1alpha/Myc-hnRNPs/PKM2 glycolysis signaling network could be targeted for the treatment of cancer caused by an aberrant RTK/PI3K/AKT/mTOR signaling pathway, mTOR signaling was activated in the majority of platelet-derived growth factor receptor [alpha] mutant and in wild-type Gastrointestinal stromal tumors cases., These results indicate that mTOR signaling is involved in visfatin-induced angiogenesis., the basis for enhanced activity of mTOR inhibitors in non-Hodgkin's lymphomas may be the lack of compensatory activation of AKT and eIF4E phosphorylation in lymphoma cells, Rheb inactivation by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1, Activation of mTORC1 results in stimulation of protein synthesis and thus cell growth via targeting multiple critical effectors of both the efficiency of translation by existing ribosomes and the synthesis of new ribosomes., The ROS-c-Src kinase-mTOR pathway played a central role in the signaling pathway that linked albumin to epithelial mesenchynal transition and endoplasmic reticular stress., The data demonstrate that up-regulation of mTOR activity and activation of both subunits are required for vascular endothelial cell proliferation induced by in vitro and in vivo chronic hypoxia., Studies suggest that dual PI3K and mTOR inhibition using NVP-BEZ235 may be an effective novel therapeutic approach in patients with ovarian cancer., Genetic variability of the mTOR pathway and prostate cancer risk., Findings suggest that the miR-99a-mTOR/FGFR3 pathway is crucial for controlling tumor growth in a wide range of human cancers that harbor upregulation of the Src-related oncogenic pathways., Single nucleotide polymorphisms in mTOR gene is not associated with colorectal cancer., These studies identify the molecular mechanism by which mTORC1 affects GSK3, mTOR Signalling in Health and Disease., The TOR pathway controls another aspect of Pol III transcription that is closely linked to MAF1, as it depends on the presence of MAF1., data support role for mTOR activation as a key regulator of muscle protein synthesis in response to essential amino acid availability; protein synthesis blocked by mTOR inhibitor (rapamycin); mTOR phosphorylation concomitant with protein biosynthesis, Studies indicate that the inhibition of mTORC1 by FOXO could lead to the activation of Akt via the inhibition of the negative feedback loop driven by mTORC1 and S6K1., S6K2 expression dictates tissue-specific requirement for S6K1 in mediating aberrant mTORC1 signaling and tumorigenesis, Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and FoxO4, Malnutrition impaired interferon signaling in patients with chronic hepatitis C by inhibiting mTOR and activating Socs3 signaling through Foxo3a., ULK1 contributes to mTORC1 inhibition through hindrance of substrate docking to Raptor., these results collectively demonstrate that TXNIP stabilizes Redd1 protein induced by ATF4 in response to 2-DG, resulting in potentiation of mTOR suppression., findings suggest that relative to the normal myometrium, there is indeed dysregulation of the P13K-Akt-mTOR pathway in uterine smooth muscle tumors, the inhibition of SIRT1 by mTOR fosters survival of DNA damage-induced prematurely senescent SCC cells via Bfl-1/A1 in the absence of functional p53., Treatment of human epithelial HeLa cells with mTOR inhibitor rapamycin reduced lysosomal exocytosis and Trypanosoma cruzi metacyclic trypomastigotes invasion., findings reveal that PA, via the mTOR kinase, can trigger tau phosphorylation on a site known to reduce paired helical filament (PHF) formation, observed a cellular compartment at trans side of the Golgi apparatus, TOR-autophagy spatial coupling compartment (TASCC), where (auto)lysosomes and mTOR accumulated during Ras-induced senescence; mTOR recruitment to TASCC was AA and Rag gtpase-dependent, Review of the pathogenesis of head and neck squamous cell carcinoma(HNSCC), mTOR pathway, mTOR inhibitor and the role of mTOR in HNSCC., REVIEW, knockdown of mTOR did not alter or only slightly reduced Akt (ser473) phosphorylation in phosphatase and tensin homolog deleted from chromosome 10 (PTEN)-null (LNCaP and MDA-MB-468 cells) and PTEN-positive (DU 145 and MDA-MB-231) cells, Data show that the deregulated kinase activities identified, which include the mTOR/p70S6K and ERK1/2 pathways, are potential novel molecular targets in MM., Apigenin increases CASP3 and CASP8 mRNA expression but decreases mTOR and CCND1 mRNA expression in HT29 cells., mTORC1 signaling as a downstream pathway regulated by the MID1/PP2A axis, suggesting that mTORC1 plays a key role in Opitz syndrome pathogenesis., the TSC/mTOR/HIF axis is activated by the KSHV vGPCR in Kaposi's sarcoma, which amplifies the angiogenic signal, mTOR pathway controls IL-12/IL-10 modulation by L. donovani in monocyte-dervied macrophages., Data suggest that mTOR kinase domain phosphorylation modulates the interaction of mTOR with regulatory partner proteins and augments intrinsic mTORC1 kinase activity to promote biochemical signaling, cell growth, and cell cycle progression., Case Report, Tightly controlled mTOR activity was crucial to maintaining podocyte function. Dysregulation of mTOR facilitated glomerular diseases. mTORC1 and mTORC2 complexes were important for podocyte homeostasis., Acute manipulation of eccentric exercise velocity does not seem to differently influence intracellular hypertrophy signaling through the Akt/mTORCI/p70S6K pathway., There might be a role for the Notch1 and mTOR pathways in the pathogenesis and therapy of plasmablastic lymphoma., Our work clarifies how mTORC1 inhibits growth factor signaling and opens new areas of investigation in mTOR biology, Polymorphisms of FRAP1 and PDGFRA were associated with corneal curvature in Asian populations., Letter, autophagy contributes to the anti-apoptotic function of the PML-RARalpha protein through inhibiting the Akt/mTOR pathway, The induction of autophagy by hepatocystin deficiency is mediated through mammalian target of rapamycin (mTOR)., Metastases in most subcellular compartments showed comparable and stronger expression for pAKT, pmTOR, and PTEN than primary renal cell carcinomas (PRCCs)., A more active PI3K/Akt/mTOR signaling pathway was also detected in TGFBI-depleted cell lines., mTOR signalling is transiently activated by leucine within human myotubes independently of insulin stimulation. Protein abundance of total mTOR is not affected by either leucine or insulin., Activation of the PI3K/Akt/mTOR pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder., mTOR expression in laryngeal SCC may be useful for the detection of patients at higher risk for recurrence., mTOR/AKT inhibition by temsirolimus decreased endometriotic cell proliferation both in vitro and in vivo in a mouse model of deep infiltrating endometriosis, Studies indicate an integral role for mTOR in the differentiation of T helper cell subsets and the development, maturation and antigen-presenting capacity of DCs in both mice and humans., These data show that human cytomegalovirus maintains mTOR activity in an amino acid- and Rag-independent manner through the colocalization of mTOR and Rheb-GTP., This study reveals a novel role for the TSC1/TSC2 complex and mTORC1 in sensing variations in ambient pH., There are significant differences in the expression of some of the mTOR-related tumor suppressors and oncogenes which could be associated with the pathogenesis of ovarian cancer., S6K1 and mTOR regulate Rac1-driven platelet activation and aggregation., important role in dental pulp stem cell differentiation, Studies indicate that temsirolimus and the oral everolimus, exhibit antitumor effects through inhibition of the mammalian target of rapamycin (mTOR) pathway., Studies indicate that current standard therapies focus on inhibiting angiogenesis via VEGF pathway (sorafenib, sunitinib, pazopanib, and bevacizumab) or mTOR pathway (temsirolimus and everolimus)., These results point to Sindbis virus replication-mediated activation of IRF3, independent of mTOR function, Studies indicate that mTOR forms two different multi-protein complexes mTORC1 and mTORC2, while mTORC1 activity is sensitive to the selective inhibitor rapamycin, and mTORC2 is resistant., DA6034 has the ability to heal scratch wounds, which may result from an increase in gastric epithelial cell migration mediated by PI3K-Akt-dependent activation of the mTOR pathway., ULK1 negatively regulates the kinase activity of mTORC1 and cell proliferation in a manner independent of Atg5 and TSC2, There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma, EGFR and mTOR signaling pathways are deregulated in ES., The pattern of expression of p-MTOR in papillary thyroid carcinomas may serve as a diagnostic/prognostic marker and a potential therapeutic target., Studies indicate there are four individual genes shown to impact life span and the aging process, Immunoblotting showed a high degree of Akt and mTOR phosphorylation in tumor samples compared with that in non-neoplastic tissue, LKB1-AMPK negatively regulated mTOR function in tumor., The knockdown of JAK1 significantly inhibits tumourigenicity of the A549 cell line and demonstrates that crosstalk between the JAK1 and PI3K/mTOR pathways is involved, Aberrant expressions of p-AKT1 and p-MTOR in intrahepatic cholangiocarcinoma were associated with a favorable prognosis, possibly in a PTEN-independent manner., Both mTOR and hypoxia-induced pathways were activated in primary and metastatic clear cell renal cell carcinomas., phosphorylation of PRAS40 is critical for the activation of mTOR in CNI-induced VEGF overexpression and renal cancer progression., These results indicate that HLA-G is associated with activation of phosphatase SHP-2, which inhibits the mTOR pathway and favors the inhibition of the cell-cycle entry of human-activated T cells., Aberrant hyperactivation of mTOR as a consequence of gene mutations in mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADalpha has been linked to developmental cortical malformations, epilepsy and neurobehavioral disabilities. (Review), mTOR signaling plays an important role in Epo-mediated bone homeostasis., dissociation of PRAS40 from insulin-stimulated 4E-BP protein binding to mTORC1 and enhanced mTORC1 substrate binding results from Akt and mTORC1 activation and makes little or no contribution to mTORC1 signaling, Syk-mTOR pathway is involed in follicular lymphoma cell invasion and angiogenesis., Data demonstrate a new role for mTOR in CXCL12-induced T cell migration, and enrich the current knowledge regarding the clinical use of rapamycin., Activation status of mTOR in T-lymphocytes influences not only lymphocyte activation and signal transduction but also regulates autoimmunity, immune tolerance, T cell subsets, and cell differentiation. [REVIEW], CREG induces endothelial cell migration by activating the integrin-linked kinase/AKT/mTOR/VEGF(165) signaling pathway., The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis., mTOR as a potential predictor for identifying LSCCs at higher risk of early recurrence after postoperative RT., AZD8055 inhibits mTOR kinase and ULK1 phosphorylation to induce autophagy whose pro-survival effect is due, in part, to down-regulation of p62., These findings indicate that the combined inhibition of mTORC1 and MNK may prove beneficial in the treatment of cutaneous T-cell lymphoma and other malignancies., These findings, representing the first genomewide search for variants influencing human protein phosphorylation, provide useful information about the PI3K/AKT/mTOR pathway., Mammalian TOR (mTOR) is activated in response to nutrients, growth factors and cellular energy. Dysregulated mTOR signaling has been implicated in major disease. [Review], Nuclear phospho-mTOR was found more frequently in triple-negative than non triple-negative breast cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC, the kinase domain of mTOR is required for the functional activity of mTORC2, and it controls integrity of mTORC2 by maintaining the protein stability of SIN1., Review, the mTOR rs2536 polymorphism is involved in the susceptibility to childhood acute lymphoblastic leukemia in a Chinese population, Akt/mTOR might be effective targets to overcome the resistance to IGF-1R mAbs in head and neck squamous cell carcinoma and non-small cell lung carcinomas., p62 is a key regulator of nutrient sensing in the mTORC1 pathway, Early use of immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for incisional hernia development after liver transplantation., the 5'-Adenosine monophosphate-activated protein kinase--mammalian target of rapamycin axis is a therapeutic target for age-related macular degeneration, Toll-like receptor 4 is up-regulated by mTOR activation during THP-1 macrophage foam cells formation., mTOR drives its own activation via SCF(betaTrCP)-dependent degradation of the mTOR inhibitor DEPTOR, DEPTOR accumulates upon glucose deprivation and mTOR inhibition to induce autophagy., mTOR generates an auto-amplification loop by triggering the betaTrCP- and CK1alpha-dependent degradation of DEPTOR, The expression of mTOR and p-mTOR is extensive in well differentiated Pancreatic neuroendocrine tumors (PNET) patients., amino acids stimulate PLD1 translocation to the lysosomal region where mTORC1 activation occurs in an hVps34-dependent manner, and this translocation is necessary for mTORC1 activation, reduced TLR-4-mediated TNF-alpha release in alveolar macrophages from asymptomatic HIV+ persons is attributable in part to increased mTOR activation., AMPK, Akt and mTOR pathways have roles in resveratrol-enhanced prostate cancer cell response to ionizing radiation, Data present a novel pathway for the regulation of Ca(2+) signaling and PASMC proliferation involving activation of Akt/mTOR and upregulation of STIM1/Orai1., Studies form the basis for further clinical testing of mammalian target of rapamycin (mTOR) complexes TORC1/2 inhibitors in multiple myeloma., Data show that mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) are up-regulated in neoplastic and developing immature mast cells compared with their terminally differentiated counterparts., results provide a first rationale and justification for targeting the ETV6/RUNX1 fusion gene and the PI3K/AKT/mTOR pathway therapeutically, Adiponectin could attenuate renal dysfunction associated with mesangial cells disorders through AMPK-mTOR signal pathway., The absence of and/or a low expression of PTEN and activated mTOR may play an important role in the development of non-small cell lung cancer., Studies indicate that mTOR phosphorylation of the 4E-BPs (4E-BP1 is the major epithelial cell form) promotes cap-dependent mRNA translation., Report activation of mTOR signalling in young and old human skeletal muscle in response to combined resistance exercise and whey protein ingestion., the mTOR-HIF-1alpha-VEGF pathway affects the progression of oral squamous cell carcinomas, We present an alternative view to mTOR complex formation and function, which envisions mTOR regulation and signal propagation as a reflection of cell type- and basal state-dependent conditions. [Review], mTORc1 inhibition reduces eIF4F complex formation, and depresses translocation of TOP mRNAs on polysomes. Downregulation of eIF4E and overexpression of 4E-BP1 induce rapamycin sensitivity, Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics., High mTOR phosphorylation is associated with intrahepatic cholangiocarcinoma., miR-376b controls autophagy by directly regulating intracellular levels of two key autophagy proteins, ATG4C and BECN1., These findings suggest that mTOR pathway is activated in HIV-induced enhanced tubular cell protein synthesis and contributes to tubular cell hypertrophy., An essential role of mTORC1 in autophagy inhibition in cell-free system in which, membrane association of Barkor/Atg14(L), a specific autophagosome-binding protein, is suppressed by cytosol from nutrient-rich medium, is shown., Misregulation of mTOR signaling occurs in fragile X syndrome., mTOR probably influences the aggressive laryngeal carcinoma (LSCC) phenotype in elderly patients and its expression in elderly LSCC cases can be considered a prognostic marker potentially useful for identifying patients at high risk of disease recurrence, The results defined the TSC2-mTOR pathway as a key determinant in the differentiation of monocytes into M2 phenotype tumor-associated macrophages that promote angiogenesis., The overexpression of mTOR and p-mTOR may play important roles in colorectal carcinogenesis with relations to the degree of differentiation, invasiveness and metastasis., IQGAP1 modulates mTORC1-S6K1-->Akt1 signaling to control cell proliferation., Bed rest in older adults significantly attenuated the essential amino acid-induced increase in muscle protein synthesis with a mechanism involving reduced mTORC1 signaling and amino acid transporter protein content., Akt/mTOR is akey signaling componenet through which c-Met protects multiple myeloma cells fro themotherapy-induced growth inhibition and apoptosis., Dual inhibition of PI3K/mTOR in ovarian cancer-spheroids leads to death of inner matrix-deprived cells, whereas matrix-attached cells are resistant., Overexpression of mu-opioid receptor increases Akt and mTOR activation, cell proliferation, and extravasation in experimental human bronchoalveolar carcinoma., When nutrients are present, phosphorylation of TFEB by mTORC1 inhibits TFEB activity., Arachidonic acid is an effective intracellular stimulus of mTOR and Arachidonic acid-activated mTOR plays critical roles in angiogenesis and tumorigenesis of breast cancer., This review summarizes the regulation and potential function(s) of PRAS40 in the complex Akt- and mTOR-signaling network in health and disease, Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion, summarizes current knowledge of mTOR and AMP-activated protein kinase pathways in regulating energy balance; reviews data on the convergence between these two pathways; discusses relevance to metabolic diseases [REVIEW], mTOR and protein phosphatase 2A catalytically control the constitutive nuclear import of latent STAT1 by KPNA1, which are key modulators of STAT1 expression and apoptosis., results suggest that the mTORC2 pathway is an essential downstream branch of TGF-beta signaling, and represents a responsive target to inhibit epithelial-mesenchymal transition and prevent cancer cell invasion and metastasis, Induction of autophagy by palmitic acid via protein kinase C-mediated signaling pathway independent of mTOR (mammalian target of rapamycin)., High mTOR expression is associated with HPV-associated oral and cervical squamous carcinomas., Birt-Hogg-Dube syndrome-associated pulmonary cyst may be considered a hamartoma-like cystic alveolar formation associated with deranged mTOR signaling., Data suggest that Smads 1, 5 and 8 as potential prognostic markers and therapeutic targets for mTOR inhibition therapy of prostate cancer., Human TERT (telomerase reverse transcriptase - the rate-limiting component of telomerase), heat shock protein 90, Akt, p70 S6 kinase (S6K) and mammalian target of rapamycin (mTOR) form a physical and functional complex with one another., Studies indicate that understanding mTOR network circuitry will provide insight into its deregulation in diabetes, cancer, and cardiovascular disease, but modeling in silico to elucidate how insulin activates mTORC2 remains poorly defined., Together, these observations suggested that hepatitis C virus infection activates the mTOR/S6K1 pathway in inhibiting IRS-1 function and perturbs glucose metabolism via downregulation of GLUT4 and upregulation of PCK2 for insulin resistance., Data indicate that in arecoline treated oral squamous cell carcinoma cells, elevated levels of p21 and p27 could be downregulated through the reactive oxygen species/mTOR complex 1 (ROS/mTORC1) pathway., Targeting PI3 kinase/AKT/mTOR signaling in cancer., mTOR is a novel powerful regulator of EAAT3 and may thus contribute to protection against neuroexcitotoxicity., found that osmotic stress activates mTORC1 kinase activity in a JNK-dependent manner. Our findings suggest that the molecular link between JNK and Raptor is a potential mechanism by which stress regulates the mTORC1 signaling pathway, mTOR complex 1-mediated anti-inflammatory programs in intestinal CD11c+CD11b+ dendritic cells are found to limit intestinal inflammation., The reduced NF-kappaB levels led to the decreased phosphorylation of mTOR signaling., PKM2-expressing cells can maintain mammalian target of rapamycin complex 1 activity and proliferate in serine-depleted medium, but PKM1-expressing cells cannot., In this review, we summarize recent findings on mTORC1 and its regulation in skeletal muscle in response to resistance exercise, alone or in combination with intake of protein or amino acids. [review], the deubiquitinase USP9X as a novel mTORC1 and -2 binding partner that negatively regulates mTOR activity and skeletal muscle differentiation., The mTOR pathway could be a good target to enhance therapy effects in certain types of thyroid carcinoma, namely in those harboring the BRAF(V600E) mutation., This review highlights how diverse signals from the immune microenvironment can guide the outcome of T cell receptor (TCR) activation through the activation of the mTOR pathway., PP242 mTOR inhibitor activates ERK in multiple myeloma cells via a target of rapamycin complex 1 (TORC1)/eukaryotic translation initiation factor 4E (eIF-4E)/RAF pathway and activation is a mechanism of resistance, Expression of pAkt and mTOR expression is more significantly associated with adenocarcinoma than squamous cell carcinoma of the lung, cells undergoing senescence progression but not the ones in quiescence maintained high mTOR and low autophagy activities, Active TFEB also associates with late endosomal/lysosomal membranes through interaction with the LAMTOR/RRAG/MTORC1 complex., The TNF-alpha-mediated in vitro RPE cell migration mainly requires Akt/mTORC1, but not mTORC2 signaling. The results of this study may lead to indentify novel signaling targets against PVR., Chronic modulation of AMP-Kinase, Akt and mTOR pathways by ionizing radiation., Targeting mTOR in mesial temporal lobe epilepsy may provide new pathways for the medical therapy of epilepsy, Data suggest that phosphoinositide-3-kinase/Akt and mammalian target of rapamycin (mTOR) pathway signaling differentially regulate phospho-Mst1-Thr-120/Thr-183., This review of the recent literature describes the clinical features, genetic mutations, and neurobiology associated with dysregulation of mTOR neurogenetic disorders and abnormalities in synaptic plasticity and mTOR signaling., interaction of the FRB domain with PA and how it is influenced by the surrounding membrane environment, Report ambiguous differentiation and mTOR pathway dysregulation in subependymal giant cell astrocytoma., 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., Together, these results suggested that hepatitis C virus induces autophagy by upregulating Beclin1 and activates mTOR signaling pathway, which in turn may promote hepatocyte growth., levels of EphB4, mTOR and Akt were distinctly lower than those in other groups. It was concluded that suppression of EphB4 may inhibit the growth of ovarian cancer cells by downregulation of the PI3K/Akt/mTOR pathway., Data show that miR-21 regulates activation of mTOR in renal cancer cells., Report preclinical absorption, distribution, metabolism, and excretion properties of mTOR inhibitor GDC-0980., Together these results suggest that PI(3,5)P(2) is an essential mTORC1 regulator that defines the localization of the complex., 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., Considering the potential capability for mTOR in regulating the repair and survival mechanisms of hypoxic or ischemic brain injury, mTOR may be a novel target for neuroprotective treatment--{REVIEW}, mTOR is activated in medullary thyroid carcinoma, particularly in lymph node metastases., Studies suggest that a dynamic/oscillatory activity of intracellular metabolism, through mTOR kinase modulation, might represent a shift in understanding the molecular mechanisms governing Treg cell tolerance., mTOR activation is associated with sclerotic hippocampus., mTOR could directly phosphorylate HSF1 on serine 326, a key residue in transcriptional activation., RSK regulates activated BRAF signalling to mTORC1 and promotes melanoma growth, Advancing age is associated with gene expression changes resembling mTOR inhibition, The association between single nucleotide polymorphisms (SNPs) of PTEN/AKT/mTOR genes and prostate cancer (PCa) in Chinese population, was examined., mTOR promotes commitment to glycolytic metabolism after exposure to lipopoysaccharide (LPS) in mouse but not human dendritic cells., Increased SCF/c-kit by hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells via regulating the phosphorylation of mTOR., Data provide information for developing new therapeutics targeting PI3K/Akt/mTOR signaling pathway in autoimmune diseases like psoriasis and rheumatoid arthritis., Phosphorylated mammalian target of rapamycin expression is independently associated with the response to chemoradiotherapy and prognosis of patients with esophageal squamous cell carcinoma treated with preoperative chemoradiotherapy., LOX-1 up-regulation induced by AGE-BSA was a receptor mediated through RAGE and is via the PI3K/PDK1/mTORC2 pathway, study examined association of candidate polymorphisms in m-TOR, Raptor and p70S6K, sirolimus dose and exposure with sirolimus-induced adverse events in kidney transplant recipients; results provide evidence of an association between an m-TOR haplotype and a decrease in haemoglobin in renal transplant recipient, High mTOR expression is associated with ovarian granulosa cell tumor., loss of p(Ser2448)-mTOR expression is a marker for activated AKT/mTOR signaling., Oridonin inhibiting activations of LYN (one of SRC family kinases) and ABL and their downstream Akt/mTOR, Raf/MEK/ERK and STAT5 pathways., we tested the capacity of the mammalian target of rapamycin (mTOR) inhibitor RAD001 to augment the cytotoxicity of low and high-LET radiation in these cells., Leucine-induced mTORC1 signaling in human fibroblasts is not mediated by a specific leucine metabolite. MAP4K3 expression is required for leucine-induced mTORC1 activation in human primary fibroblasts., These results suggest that mTOR activity is characteristic in most non-germinal center-derived diffuse large B-cell lymphomas with potentially variable mTOR-inhibitor sensitivity., expression of mTOR in patients with diffuse large B-cell lymphoma was associated with male gender, older age, and shorter survival, Pathway analyses suggested transcriptomal upregulation of mTOR-related genes by MYCN in neuroblastoma, ADAMTS9 acts as a functional tumor suppressor in gastric cancer through inhibiting oncogenic AKT/mTOR signaling pathway, Explored deregulation of miRNAs targeting mTOR kinase (miR-99a, miR-100 and miR-199b) in endometrioid endometrial carcinoma. mTOR kinase expression was increased in EEC tissues and was accompanied by decreased expression of all three miRNAs., Increased phospho-mTOR expression in megakaryocytic cells derived from CD34+ progenitors of essential thrombocythaemia and myelofibrosis patients., Phosphorylated-mTOR and the ratio of phosphorylated-mTOR/mTOR are closely linked to tumor progression and represent independent prognostic factors in esophageal squamous cell carcinoma., SDF-1alpha-CXCR4 signaling represents a microenvironmental factor that can maintain mTOR pathway fidelity to promote resistance to mTOR-targeted therapy in pancreatic cancer by a variety of mechanisms., Mammalian target of rapamycin, PTEN, and beta-catenin are independently involved in different molecular subtypes of endometrial carcinoma with diverse patients' prognosis and support their distinctive treatment based on targeted drugs., Inhibiting the mammalian target of rapamycin (mTOR) with rapamycin increases the clonogenic capacity of primary human oral keratinocytes and their resident self-renewing cells by preventing stem cell senescence., Different cellular tools, including adult stem cells, embryonic stem cells or induced pluripotent stem cells could be used to investigate the role of mTOR in mammalian stem cell biology., Data suggest that sustained hyperinsulinemia (prolonged infusion of insulin) without amino acid supply does not stimulate synthesis of mitochondrial proteins or ATP production in skeletal muscle; phosphorylation of c-Akt (but not mTOR) is stimulated., The nuclear expression of p-mTOR, p-4E-BP1 and p-p70S6K was associated with biological behaviors (invasiveness) of ameloblastomas, and p-mTOR was an independent predictor of them., Downregulation of miR-144 is associated with colorectal cancer progression via activation of mTOR signaling pathway., mTORC1 activation requires dynein-dependent transport to a position in the cell where it can be activated, upregulation of miR-101 in response to laminar shear stress (LSS) contributes to the suppressive effects of LSS on mTOR expression and endothelial cells proliferation., Exercise training increased AMPKalpha1 activity in older men, however, AMPKalpha2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not affected, thioridazine regulates endothelial cell functions that are relevant to angiogenesis through the suppression of the alphavbeta3/FAK/mTOR signaling pathway, LKB1 inhibited Yap independently of either AMPK or mTOR activation, These observations suggest that recruitment of mTOR by prefrontal 5-HT(6) receptors contributes to the perturbed cognition in schizophrenia, offering new vistas for its therapeutic control., amino acid starvation regulates autophagy in part through an increase in cellular Ca(2+) that activates a CaMKK-beta-AMPK pathway and inhibits mTORC1, which results in ULK1 stimulation, sphingolipid rheostat in ceramide-CAPPs and S1P-S1P(3) signaling modulates autophagy and its associated cell death through regulation of the mTOR pathway., The mTOR pathway not only plays a role in the regulation of disease and aging in animal models, but also in human health and longevity., Cardiac and skeletal muscle pathology in transgenic mice can be attributed to elevated MTORC1 signaling leading to impairment of autophagic flux., mTOR significantly up-regulates the neutrophil respiratory burst of patients with cirrhosis by p38-MAPK activation., We found dysregulation of mTOR pathway members in urinary bladder plasmacytoid urothelial carcinoma., Phosphatidylinositol 3-kinase-protein kinase B-mTOR signaling is required for plasmacytoid dendritic cell development and survival., The mTOR Ser2481 autophosphorylation should be added to the growing list of phospho-active forms of proteins of the AMPK/mTOR/S6K1 signaling axis that reside at the mitotic and cytokinetic apparatus., HIF-2alpha/mTORC1/SLC7A5 pathway mediates proliferation and tumor promoting properties of HIF-2alpha., 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 the massive poly(ADP-ribose) (PAR) synthesis following PARP-1 activation leads to the modulation of mTORC1 pathway., Mammalian target of rapamycin (mTOR) signaling network in skeletal myogenesis., Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies., increased autophagy, secondary to persistent PERK and LKB1-AMPK signaling, can robustly protect cells from anoikis and promote luminal filling during early carcinoma progression, Over-expression of phosphorylated mammalian target of rapamycin is associated with poor survival in oesophageal adenocarcinoma., mTORC1 and mTORC2 regulate human trophoblast amino acid transporters by modulating the cell surface abundance of specific transporter isoforms, Analyzed the effects of dual inhibition of mTOR and AKT on the proliferation of HCC cell lines & measured feedback activation of each AKT isoforms after mTOR inhibition in HCC cell lines and enzymatic activity in primary samples from HCC patients., These data suggested hepatitis C virus inhibited the AKT-TSC-MTORC1 pathway via endoplasmic reticulum stress, resulting in autophagy., Results indicate that MTOR is a direct target of miR-99a., In non-small cell lung cancer cells, LKB1/AMPK signaling negatively regulates mTOR activity and contributes to cell growth inhibition in response to energy stress., MARK4 is a new negative regulator of mTORC1, the functional MTOR promoter rs2295080 variant affects RCC susceptibility by modulating the endogenous MTOR expression level in renal cell carcinoma patients, In this review, signal-transducing kinase mTOR reacts to amino acid deprivation by inhibiting general protein translation., the mTOR pathway is implicated in the Studies indicate that tumorigenesis of multiple cancer types and its deregulation is associated with familial cancer syndromes., HMGA2 overexpression induced a PI3K/Akt/mTOR/p70S6K cascade, which in turn suppressed the expression of p16(INK4A) and p21(CIP1/WAF1) in human umbilical cord blood-derived stromal cells., Studies indicate roles of mTORCs in the cellular environment at multiple levels., Data suggest that dietary protein supply (but not glutamine alone) up-regulates protein biosynthesis in duodenal mucosa in healthy subjects; this up-regulation is mTOR-independent., The activation of GPR10 by its cognate ligand, prolactin releasing peptide, promotes PI3K-AKT-mTOR pathways and cell proliferation specifically in cultured primary leiomyoma cells., ULK1-dependent autophagy degrades BNIP3 via MTORC1 and AMPK, No significant correlation was found between mTOR activation and any of the morphopathological features in the studied samples, Data suggest mechanisms of carcinogenesis by heavy metals involve increased activation of signaling pathways involving mTOR, PI3K/AKT (phosphatidylinositol 3-kinase/proto-oncogene protein c-AKT), and EGRF (epidermal growth factor receptor). [REVIEW], Data suggest that mTOR is a critical integrator in complex network that regulates multiple signaling pathways in normal and cancer cells; mTOR appears to mediate tumorigenesis and thus is a potential target for antineoplastic therapies. [REVIEW], sEcad contributes to skin carcinogenesis via association with the HER/IGF-1R-family of receptors and subsequent activation of the MAPK and PI3K/Akt/mTOR pathways., beyond the pivotal position of mTOR to relay the oncogenic signals from the upstream phosphatidylinositol 3-kinase/Akt pathway in human cancer, mTOR is capable potentially of playing a direct role in human tumorigenesis if mutated., REVIEW, role as central regulator of CD4 and CD8 T cell metabolism, differentiation, and trafficking., In the course of autophagy, lysosomal function is upregulated via a dual mechanism involving mTORC1 suppression and autophagosome-lysosome fusion., The expression of phosphorylated mTOR was determined by ScanScope XT and ACIS III and compared with the manual analysis by two observers., Our results suggest that XLID CUL4B mutants are defective in promoting TSC2 degradation and positively regulating mTOR signaling in neocortical neurons., The data suggest that combined assessment of constitutive gammaH2AX expression, mitochondrial activity and mTOR signaling provides an adequate gamut of cell responses to evaluate effectiveness of gero-suppressive agents., Studies suggest that targeting mTOR dysregulation in the hematopoietic stem cells (HSC) may help to break the vicious cycle between cytopenia and autoimmune diseases., Data show that potential therapeutic benefits of mammalian target of rapamycin (mTOR) inhibition may be the result of effects on differentiated leukemic cells and may be potentially achieved only in the chronic phase of the disease., at the core of insulin resistance in human adipocytes is attenuation of a positive feedback from mTORC1 to the insulin receptor substrate-1, Upregulation of HO-1 is accompanied by activation of p38MAPK and mTOR in human oesophageal squamous carcinoma cells., Insulin upregulates mTOR in the placenta and interferes with the amino acid uptake and cell growth., mTORC1 polymorphism is associated with gastric cancer., Studied the effect of the mTOR inhibitor RAD001 on NPC cell lines and found the main mechanism of the mTOR inhibitor RAD001 in nasopharyngeal carcinoma cells was apoptotic, not autophagic cell death., Data indicate that combining sorafenib with everolimus resulted in complete abrogation of both mTORC1 and mTORC2 in mice xenografts., a unique role for PML in mTOR and EGFR inhibitor resistance and provide a strong rationale for a combination therapeutic strategy to overcome it., Results suggest that 13-197 targets IKKbeta and thereby inhibits mTOR and NF-kappaB pathways., mTOR-dependent proliferation defect in human ES-derived neural stem cells affected by myotonic dystrophy type 1., The high expression of mTOR and 4EBP1 is closely related with clinicopathology and lymph node metastases in laryngeal carcinoma., Mechanistic target of rapamycin (mTOR) dependent regulation of thioredoxin interacting protein (TXNIP) transcription in hypoxia., The prevalence of positive p-mTOR in ovarian clear cell carcinoma was 87.9%., Single nucleotide polymorphisms in mTORC1 gene is associated with esophageal squamous cell carcinoma., findings show under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated; in this condition, AMBRA1, interacting with TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its stabilization, self-association and function, hypoxia can influence mTORC1 signaling as a switch for a phase transition in cancer cells, we identified 3HOI-BA-01 as a novel and effective mTOR inhibitor., There is a significant downregulation of mTOR, DEPTOR, and Raptor in preterm labouring myometria when compared to non-pregnant tissues taken from the same area., Immunohistochemical expression of phospho-mTOR is associated with poor prognosis in patients with gallbladder adenocarcinoma., Data indicate that concurrent BRAF and PI3K/mTOR blockade results in induction of apoptosis., The mTOR promoter polymorphism rs2295080 was significantly associated with gastric cancer risk., MTOR activity may be associated with poor prognosis in acute lymphoblastic leukemia., Mammalian target of rapamycin (mTor) mediates tau protein dyshomeostasis, Constitutively active mTORC1 decreased translation fidelity by increasing the speed of ribosomal elongation., effect of p-mTOR in OS of OSCC suggests that this marker may serve as reliable biological marker to identify high-risk subgroups and as a guide to therapy. the high expression of p-mTOR suggests this protein may be promising therapeutic target in OSCC., Deeper insights into the molecular interplay of FoxO1/mTORC1-mediated nutrient signalling are thus of critical importance to understand the impact of Western diet on the promotion of epidemic acne and more serious mTORC1-driven diseases of civilization., Activation of the mTOR pathway might be used to provide prognostic information in patients with high-risk non-muscle invasive bladder cancer., 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., Muscle biopsies were collected before and 1 and 3 h post resistance exercise and phosphorylation of mTOR (Ser(2)) increased 2-fold (P < 0.05) and that of S6K1 (Thr(3)) 14-fold (P < 0.05)., co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors, the ability of ciclopirox to inhibit mTOR is specific to ciclopirox because neither iron chelators nor other eIF5A inhibitors affect mTOR activity, even at high doses., we review recent advances in the understanding of the molecular mechanisms involved in white and brown differentiation programs focusing on AMPK and mTOR signaling pathways., Report a synthetic lethal interaction between PI3K/mTOR and MEK inhibitors in rhabdomyosarcoma., Signalling pathways regulating muscle mass in ageing skeletal muscle involve roles in the IGF1-Akt-mTOR-FoxO pathway., PTEN and MTOR expression correlate with clinicopathological features in pancreatic neuroendocrine tumors., Dysregulated autophagy in alpha-galactosidase A-deficient (Fabry's disease) podocytes may be the result of deficient mTOR kinase activity., Targeting mTOR activity may be a potential therapeutic tool in lymphomas, the function of mTOR, its genetic regulation in pediatric neuroblastoma, and its value as a target for inhibition by anticancer agents for patients with NB. [review], These findings imply a direct role for TORC1 in epilepsy. Here, we investigate the effect of increased TORC1 signaling induced by acute biallelic deletion of Tsc1 in healthy adult mice., Interaction of vitronectin with integrin alphavbeta3 results in the continued activation of the kinase mTOR., Abnormal activation of mTOR may contribute directly to a defect in autophagy in focal cortical dysplasia and tuberous sclerosis., Data suggested altered mTOR signaling and mitochondrial function-each canonical regulators of longevity-in cells expressing DeltaNp53, NBS1 interacts with the mTOR/Rictor/SIN1 complex through the a.a. 221-402 domain and contributes to the activation of Akt activity., The study shows that mTOR is likely to be involved in the development and progression of colorectal cancer and is linked to cancer initiation, invasiveness, and progression., signaling from mitochondria to the nucleus is influenced by mammalian target of rapamycin (mTOR) activity via changes in autophagy and p62/SQSTM1 turnover., Utilizing mTOR rechallenge as an integral part of sequential treatment strategies in mRCC., These results demonstrate that the activities of AR and mTOR pathways are maintained by KLK4, which may thus be a viable target for therapy, These data establish mTOR as a key mediator of RET-mediated cell growth in thyroid cancer cells and provide a rationale for combinatorial treatments in thyroid cancers with oncogenic RET mutations., 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., these findings present a novel mechanism of ROS-regulated apoptosis and autophagy that involves Akt-mTOR signaling in prostate cancer cells with mutant p53 exposed to DHA., [review] Upregulation of the mTOR signaling pathway is thought to play an important role in major pathological processes of Alzheimer's disease., evidence suggests that many processes attributed to the Akt pathway in myelination depend, at least partly, on mTOR signalling, 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, We demonstrate elevated mTOR complex 1 (mTORC1) activity in alveolar soft part sarcoma independent of mTOR complex 2 (mTORC2) activation., Inactivation of HIF-1, by silencing its inducible alpha subunit, significantly decreases mTOR S2448 phosphorylation caused by ligand-dependent activation of human myeloid leukemia cells., Data indicate a nitrosative-stress signaling pathway that engages ATM, LKB1, AMPK and TSC2 tumor suppressors to repress mTORC1 and regulate autophagy., Data indicate that sunitinib inhibited TORC1 in endothelial cells in a Tsc1/Tsc2-dependent manner., Milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes.[Review], High phosphorylated mTOR expression is associated with non- small cell lung cancer., Ionizing radiation promoted mTOR expression and activation in pancreatic cancer cells through reducing miR-99b expression, which negatively regulated mTOR., Histolopathological and clinical information including tumour stage, invasion characteristic and endocrine status were analysed against the gene transcript expression of mTOR, RAPTOR and RICTOR., TRAF6-catalyzed K63 ubiquitination of mTOR regulates mTORC1 activation by amino acids., These results identify mTOR activation to be a trigger of IL-4 production and necrotic death of double-negative T cells in patients with systemic lupus erythematosus., results show that ATF4-regulated SESN2 expression presents a new link between ER stress and mTOR inhibition and autophagy., Findings suggest that mTOR signaling is activated in cancer stem cells (CSCs)-like cells and plays an important role in nasopharyngeal carcinoma (NPC) growth., mTOR SNPs may contribute to the risk of Prostate cancer in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies., BRAF V600E-mutated protein may be valuable in the diagnostic evaluation of these glioneuronal lesions and the observed association with mTOR activation may aid in the development of targeted treatment involving specific pathogenic pathways, Dysregulation of the mammalian target of rapamycin pathway occurs in chromophobe renal cell carcinomas., results suggest that 13-197 as a single agent disrupts the NF-kappaB and mTOR pathways leading to suppression of proliferation and increased apoptosis in malignant MCL cells including reduction in tumor burden in mice., The growth factor-mediated restriction point can be temporally distinguished from a series of late G1 metabolic checkpoints mediated by essential amino acids, glutamine and mTOR., The mTOR complex 1 were expressed in hippocampus in patient with Alzheimer disease', Integration of mTOR and estrogen-ERK2 signaling in lymphangioleiomyomatosis pathogenesis., Data indicate that ZNF703 overexpression in MCF-7 breast cancer cells activated the Akt/mTOR signaling pathway, downregulated ERalpha, and reduced the antitumor effect of tamoxifen., study suggests that the combination of mTOR kinase and EGFR inhibitors may provide an effective treatment of colorectal carcinoma, Bleomycin induces endothelial mesenchymal transition through activation of mTOR pathway, activation of the mTOR/S6K signaling pathway plays a significant role in tumorigenesis and progression of PNET., Data indicate mTOR kinase-independent function and mechanism of Rictor in the regulation of neutrophil chemotaxis, and suggest that the small Rho GTPases Rac and Cdc42 serve as downstream effectors of Rictor to regulate actin assembly., 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., Taken together, gut microbiota-producing t10,c12 conjugated linoleic acid activate hepatic de novo lipogenesis and triglyceride synthesis through activation of the mTOR/SREBP1 pathway, with consequent lipid accumulation in HepG2 cells., Long-term treatment with TORIs does not benefit patients with ADPKD., considerably higher expression of phospho-mTOR in SCC compared to BCC is a likely explanation for their higher sensitivity to mTOR inhibitors, TBK1 interacts with mTOR and inhibits its function. mTOR inhibition induces the cell cycle arrest of prostate cancer cells and enhances chemotherapeutic resistance of PCa cells., Superoxide activates mTOR-eIF4E-Bax route to induce enhanced apoptosis in leukemic cells., Regulation of mammalian autophagy by mTOR-dependent and mTOR-independent pathways is amenable to chemical perturbations. A number of small-molecule inducers of autophagy has been identified, some of which are FDA-approved drugs, mTOR expression was correlated with EGFR expression and CD105 (a marker of microvascular density) expression in laryngeal squamous cell carcinoma., Constitutive mTOR signaling induces the formation of giant cells via phosphorylation of S6K., the expression of the fusion gene DEK-NUP214 leads to increased cellular proliferation. We show that this is dependent on upregulation of the signal transduction protein mTOR with subsequent effects on protein synthesis and glucose metabolism., A novel function for mTORC1 in maintaining the epithelial phenotype and epithelial-to-mesenchymal transition., With the lack of licensed anti-polyoma viral drugs reduction or conversion of immunosuppression remains the mainstay of therapy in patients with PyVAN., These data identify a late stage of phagocytosis and entosis that involves processing of large vacuoles by mTOR-regulated membrane fission., Feeding uninvited guests, The AKT/mTOR signaling pathway is highly activated in ALK + ALCL patients and targeting the AKT/mTOR signaling pathway might confer a great therapeutic potential in ALCL., NOTCH1 and 2 knockdown reduces the level of mechanistic target of rapamycin (mTOR) protein in the monoblastic leukemia cell line THP-1., indicate the mechanism of cross talk between the protumorigenic membrane protease MT1-MMP and the signal integrator mTOR to activate HIF-1 during normoxia., alpha6beta4 integrin and c-Src activation is important early signaling events to lead mTOR activation and cap-dependent translation of VEGF., Active mTOR pathway is associated with pediatric low-grade glioma., mTOR-mediated drug resistance to rapamycin can be reversed by increasing phosphorylation of eIF-2alpha., the ability of LPAAT-beta to regulate mTOR function, Data suggest that the combined evaluation of of potential markers in the mammalian target of rapamycin (mTOR) signaling pathway in renal cell carcinoma (RCC) would contribute to the accurate prediction of disease recurrence following radical nephrectomy., analysis of PDGFR, VEGF-C, and proteins of the mToR pathway before and after androgen deprivation therapy in prostate carcinoma, Data indicate that MLN0128 downregulated key components of the two mTOR subpathways, TORC1 and TORC2., Activated mTOR signaling is a general phenomenon in variants of progressing renal diseases and may be used as a marker of active renal disease states., 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., These data provide a novel mechanistic link of Nox4-dependent activation of mTORC2 via the energy sensor AMP-activated protein kinase to increased proliferation and survival of PAVSMCs in pulmonary artery hypertension., The activation level of the EEF1A2/PI3K/AKT/mTOR/MDM4 axis significantly influences the survival probability of hepatocellular carcinoma patients., Ghrelin stimulated the rapid phosphorylation of mammalian target of rapamycin (mTOR), P70S6K and S6., High mTOR and phosphorylated mTOR expression is associated with gastrointestinal stromal tumors, Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2) or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity, Aberrant mTOR activity in ovarian endometriotic cysts leads to alteration of endometrial cell autophagy, which is associated with abnormal apoptosis., 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., we described a novel molecular mechanism of Pdcd4 suppression in cancer cells consisting from mTOR signaling-dependent transcriptional repression of Pdcd4, Amino acids promote mTORC1 activation without altering Rag GTP charging., These findings highlight MDM2 as a potential therapeutic target to increase TKI-mediated apoptosis and imply that the combination of PI3K/mTOR inhibitor and TKI might form a novel strategy to combat TKI-resistant BCR-ABL1 positive leukemia., Depletion of luminal NADPH had also significant effect on the key proteins of mTOR pathway., Akt/mTOR was activated in 50% of the cases of Solitary fibrous tumors and was associated with receptor tyrosine kinases, which were phosphorylated at different rates. The Akt-mTOR pathway may be involved in the tumorigenesis of Solitary fibrous tumors., This study showed that PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-kappaB or MAPK signaling., Suggest enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells via targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases., Increased phospho-mTOR expression was associated with mesothelioma., Data indicate that mammalian target of rapamycin (mTOR) knockdown had a superior antiproliferative effect than acting only on mTORC1 or mTORC2., Data indicate that endogenous mTOR interacts with Gbetagamma., mTOR activity was markedly increased in p53-deficient tumors and rapamycin treatment suppressed tumor cell growth, identifying mTOR inhibition as a critical p53 tumor suppressive function, observed that miR-193a-3p/5p could inactivate the AKT/mTOR signaling pathway, The new frontier of inhibiting the mTOR pathway is to identify agents targeting the feedback loops and cross talks with other pathways involved in the acquired resistance to mTOR inhibitors, This article reviews the information available regarding the effects exerted by mTOR signaling in cardiovascular physiology and pathological states., Pseudo-hypoxic state is not necessarily caused by mitochondrial dysfunction, but instead mitochondrial dysfunction may be secondary to mTOR-driven hyperfunctions., Gal-1 overexpression increased phosphorylation of Akt, mTOR and p70 kinase., This review summarizes the current knowledge on mTOR pathway signaling in bone tissue and provides an overview on the known effects of mTOR inhibition in bone cancer, both in in vitro and in vivo models., MAF has a role in mediating crosstalk between Ras-MAPK and mTOR signaling in NF1, mTOR enhances foam cell formation by suppressing the autophagy pathway., significant emphasis has been placed on the role of mTOR pathway in SCC pathogenesis. Furthermore, some studies have demonstrated the ability of mTOR inhibitors to decrease the incidence of new SCCs in the immunosuppressed transplanted patient population, Case Report, Studied laser phototherapy imapct on cellular migration, proliferation, and activation of the mammalian target of rapamycin (mTOR) pathway., PTEN and mTOR might play an important role in the local invasiveness of sacral chordoma, unlike the other isoforms of Shc1, p66Shc appears to antagonize insulin and mTOR signaling, which limits glucose uptake and metabolism., data support the hypothesis that FSS-induced differentiation and proliferation involves the PI3K/AKT/mTOR signaling axis, through a process involving mir-132., The Akt-mTOR signaling pathway may play a limited role in the progression of prostate cancer., Which inhibits both complexes of mTOR (mTORC1 and mTORC2)., High mTOR expression is associated with drug resistance in chondrosarcoma., A feedback inhibition loop of mTORC1 onto mTORC2 plays a role in the homeostasis of E-cadherin expression in lung cancer cells., In cells expressing the VPS34-Y231F mutant, which blocks lamellipodia formation, mTOR localization at the plasma membrane and insulin-mediated S6K1 activation are reduced., number of studies have shown an association between marked deficits in synaptic proteins and dysregulation of mTOR signaling in MDD., High mTOR complex activity is associated with papillary thyroid carcinoma., Mutations in DEP domain containing (DEPDC)5, a negative regulator of mTOR, causes focal epilepsy with brain malformations., JNK contributes to the tumorigenic potential of human cholangiocarcinoma cells through the mTOR pathway regulated GRP78 induction., Rapamycin may prohibit sestrin1 downregulation through targeting mTORC2 in appeasing low shear stress induced EC oxidative apoptosis, The mTOR/Akt pathway is activated through TGFbetaRII in cerebellar granule cells, regulated by GDF15 and Kv2.1., thrombin activates the mTORC1 pathway in human platelets through PKC-mediated ADP secretion and subsequent activation of P2Y(12), in a manner largely independent of the canonical PI3 kinase/Akt pathway, NGF regulates the expression of VEGF through the PI3K/mTOR signaling pathway in human HaCaT keratinocytes., High phosphorylated mTOR expression is associated with adverse clinicopathologic parameters in gastric carcinoma., Genomic alterations with activating effect on mTOR signaling were detected in 11 of 14 specimens, offering plausible explanation for exceptional treatment response through alterations in two genes (TSC1 and MTOR)., Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program., Suggest role for PTEN/mTOR/B7-H1 pathway in immune-resistance, immune escape and progression of pancreatic cancer., Inhibition of mTOR (and PI3K) increases catalase expression only in MCF-7 breast cancer cells but not in resistance to oxidative stress cells., Reports indicate that a diverse set of cancer-associated MTOR mutations confer increased mTORC1/2 pathway activity in certain neoplasm., miR-99a antitumor activity is achieved by targeting the mTOR/p-4E-BP1/p-S6K1 pathway in human breast cancer cells., The use of mTOR inhibitors may be considered for the treatment of such tumors., Data suggest that the interacting proteins may offer targets for therapeutic interventions in diseases caused by perturbed mammalian target of rapamycin complex 1 (mTORC1) signaling., Data indicate that Rheb G63A stimulated phosphorylation of the mTORC1 substrate p70S6 kinase more strongly than wild-type, thus offering a new tool for mammalian target of rapamycin (mTOR) signaling., PI3K/mTOR dual inhibitor NVP-BEZ235 decreases Mcl-1 expression and sensitizes ovarian carcinoma cells to Bcl-xL-targeting strategies, provided that Bim expression is induced., There is a role of mTOR and its downstream modulation of autophagy in articular cartilage homeostasis., Low protein expression of p-Akt308 was associated with improved DFS and OS among patients treated with hormonal therapy following adjuvant chemotherapy. Coexpression of EGFR and p-mTOR was associated with worse OS., 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], mTORC1 controls the onset and the maintenance of pathological neuroadaptions that underlie several features of drug addiction--{REVIEW}, CaMK4-dependent activation of AKT/mTOR and CREM-alpha underlies autoimmunity-associated Th17 imbalance., High mTOR expression is associated with cervical cancer., These studies demonstrated that fisetin inhibits mTOR and p70S6K through direct binding while the observed inhibitory effect of fisetin on AKT is mediated indirectly, through targeting interrelated pathways., effectiveness of these agents to attenuate the level of constitutive mTOR signaling was tested by cytometry and confirmed by Western blotting through measuring phosphorylation of the mTOR-downstream targets including ribosomal protein S6, rapamycin combined with celecoxib could induce cell cycle arrest and apoptosis and decrease the expressions of mTOR, 4E-BP1, and p70S6K., mTORC1 expands IL-4(+) CD4(-)CD8(-) double-negative T and Th17 cells, and contracts Tregs in systemic lupus erythematosus, Disruption of mTOR signaling decreased STAT3 expression in macrophages, thus contributing to development of atherosclerosis., our data identified the PELP1-mTOR axis as a novel component of PELP1 oncogenic functions and suggest that mTOR inhibitor(s) will be effective chemotherapeutic agents for downregulating PELP1 oncogenic functions., Results suggest that up-regulated mTorC2 might be playing an important role in promoting cell survival, Letter, mTOR gene knockdown via lentivirus mediated mTOR specific shRNA resulted in a significant decrease in the viability and growth of prostate cancer cells, 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., This effect correlated with depletion of principle proteins of the Akt/mTOR and MAPK survival and proliferation pathways., Our findings demonstrate that AKT/mTOR and JNK2 signaling pathways are required for chrysotile asbestos-induced autophagy, Aberrant activation of the PI3K/Akt/mTOR axis acts in parallel to RCAN1 in phosphorylating tau, in DS and DS/AD., High mTOR expression is associated with medulloblastoma., Inflammation contributed to foam cell formation in the radial arteries of ESRD patients via the dysregulation of the LDLr pathway, which could be modulated by the activation of the mTOR pathway., proteomic view to characterize the effect of chitosan nanoparticle to hepatic cells, PI3K/AKT/mTOR is a crucial survival pathway downstream of multiple activated receptor tyrosine kinases in mesothelioma., Fundamental role of the PI3K/AKT/mTOR pathway., Data show that salvianolic acid B protects endothelial progenitor cells against oxidative stress by modulating Akt/mTOR/4EBP1, p38 MAPK/ATF2, and ERK1/2 signaling pathways., Alterations in insulin action and mammalian target of rapamycin activation have been well documented to lead to pathology in diabetic nephropathy., Aminoimidazole carboxamide ribonucleotide treatment was associated with inhibition of eukaryotic translation initiation factor 4E-BP1 phosphorylation, a marker of mammalian target of rapamycin (mTOR) pathway activity., Hyperphosphatemia induces endothelial autophagy, possibly through the inhibition of the Akt/mTOR signaling pathway, which may play a protective role against high Pi-induced apoptosis., Metformin lowers Ser-129 phosphorylated alpha-synuclein levels via mTOR inhibition and protein phosphatase 2A activation., Overexpression of mTOR is associated with papillary thyroid carcinomas., Successfully treatment of the prior fatal course of the KHE with KMP was initiated not till adding the mTOR inhibitor sirolimus to therapy., AKT-mTOR pathway is a novel component of oncogene induced DNA damage response in immortalized 'normal-like' breast cells and its suppression may contribute to growth arrest and arrest of the breast tumorigenesis, The wild genotype TT of rs2295080 mtor polymorphism was associated with increased cancer risk under dominant model in Chinese., SPAG5 upregulation relates to poor prognosis in cervical cancer patients, and SPAG5 is a regulator of mTOR activity during taxol treatment in cervical cancer., This article reviews current data on the alteration in the mTOR transduction cascade, which may contribute to common neurobehavioral disorders typical for autism spectrum disorder., Inhibition of cathepsin S activates ROS-mediated PI3K/AKT/mTOR/p70S6K and JNK signaling to induce autophagy and apoptosis., MCP-1 was shown to have a role in activation of the ER1 by phosphorylating Ser167 via the PI3K/Akt/mTORC1 signaling pathway, The expression levels of phospho-mTOR and phospho-S6RP may be potential predictive biomarkers for efficacy of everolimus in patients with metastatic renal cell carcinoma., in breast tumors where there is intact estrogen regulated signaling, mTOR is regulated by estrogen and therefore associated with an increased likelihood of responsiveness to endocrine therapy., 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)., These data suggest the presence of an activated mTOR pathway in a subset of adrenocortical tumors and a possible response to sirolimus only in certain adrenocortical carcinomas cases, The results of this study implicate hyperactive mTOR signaling as a previous unidentified signaling pathway underlying gene-expression dysregulation and cognitive deficits in Alzheimer disease., By reducing MMP-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways., the expression patterns of mTOR components in adult down syndrome hippocampus support its association with Alzheimer disease-related histopathologic, Our findings provide evidence for mTORC1 activation and FGFR1 overexpression in human fibrolamellar carcinoma, 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., Delicately balanced regulation of mTORC1 activation and action in oligodendrocytes is essential for central nervous system (CNS) myelination., Results show that thioridazine regulates endothelial cell function and subsequent angiogenesis by inhibiting VEGFR-2/PI3K/mTOR signal transduction., Data show that doxazosin inhibited the phosphorylation of VEGF receptor-2 (VEGFR-2) Akt and mammalian target of rapamycin (mTOR), and hypoxia-inducible factor 1 (HIF-1alpha) expression., The roles of the mTOR complexes in haemato-lymphopoiesis and leukemogenesis. [Review], 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., Data indicate that dual inhibition of Brutons tyrosine kinase (BTK) and mTOR serine-threonine kinases as a potential treatment for ABC-subtype diffuse large B cell lymphoma., transfecting mTOR siRNA into A549 cells significantly decreased the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) and survivin, The effect of mammalian target of rapamycin inhibition on T helper type 17 and regulatory T cell differentiation in vitro and in vivo in kidney transplant recipients., the capability of mTOR, in particular mTOR complex 1 (mTORC1), to activate stress-responsive transcription factors, and we outline open questions for future investigation., Data show that downstream of Akt protein, IkappaB kinase alpha (IKKalpha) directly phosphorylates mammalian target of rapamycin (mTOR) to drive mTORC1 activation., Phospholipase D and the maintenance of phosphatidic acid levels for regulation of mammalian target of rapamycin (mTOR)., CXCR4-CXCL12-CXCR7 regulates mTOR signaling in renal cancer cells., PTEN status in Ewing sarcoma affects cellular responses to IGFI and mTOR-directed therapy., that mTOR has an impact on the functional activities of cDCs via modulating the outcome of IFN secretion., There is a growing appreciation of mTOR in adaptive immunity for its crucial roles in keeping a proper balance between T cell quiescence and activation. (Review), Fasting increases human skeletal muscle net phenylalanine release and this is associated with decreased mTOR signaling., Rapamycin inhibition of mTOR results in feedback activation of AKT., miR-100 suppressed the expression of mTOR and IGF-1R by binding to their 3' UTR, and knockdown of mTOR or IGF-1R phenocopied the pro-autophagy effect of miR-100, indicating that miR-100 may promote autophagy by reducing mTOR and IGF-1R level., Thyroid cancer cells lose TSH/cAMP dependency of mTOR signaling and cell growth., that HTR6 plays an important role in modulating seizure activity and that the blockade of the 5-HT6 receptor/mTOR pathway could be a potential therapeutic target for epilepsy treatment, mTORC1 signalling increases the efficiency of proteasome-mediated protein degradation for both quality control and as a mechanism to supply substrate for sustained protein synthesis, MTOR regulate EMT at least in part by down regulation of RhoA and Rac1 signaling pathways., Phosphorylated mTOR signaling has a role in both initiation and progression of prostate cancer., Hence, we propose the TCM compounds, picrasidine M and acerosin, as potential candidates as lead compounds for further study in drug development process with the mTOR protein against Leigh syndrome and other mitochondrial disorders., miR-99a/mTOR pathway was involved in diaporine A-induced tumor suppression in non-small cell lung cancer cells., Studies indicate the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway in breast cancer., p-mTOR is associated with tumour size and grade, and p-mTOR expression in luminal breast tumours is associated with longer disease-free and overall survival., Our results suggest that the mTORC pathway is involved in the vascular lesions associated with the antiphospholipid syndrome., This study provides the first evidence for mTORC1/p70S6K-dependent regulation of pyrimidine biosynthesis in a relevant disease setting., Investigated the effects of mTOR-STAT3 pathway on the invasion and migration of hepatoma cells., Germline SNPs in the PI3 K-AKT-mTOR pathway were associated with breast cancer., MTOR is downregulated by MIRN100 targeting of its 3'UTR in esophageal squamous cell carcinoma., Aspirin mediates the inhibition of neuroendocrine tumor cell growth and signaling via mTOR signaling pathway., In Alzheimer's disease patients the mTOR pathway can be overactive, leading to a dysfunction of autophagy and a lack of amyloid beta clearance so the excess of amyloid beta will cause a further decrease in DEPTOR and an increase in mTOR expression., 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., Degradation of Tiam1 by casein kinase 1 and the SCFbetaTrCP ubiquitin ligase controls the duration of mTOR-S6K signaling., Mammalian target of rapamycin protein regulates the diffusion of Xrn2 from the nucleolus to the nucleoplasm under heat stress conditions., results show that mTORC1 is an important signaling intermediary in PGE2 mediated colon cancer cell growth and VEGF production., EIF4B, as a potentially key fragile point in EGFR and mTOR inhibitor synergy., 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., The findings of this study suggested that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR., GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1pathway., An association between Ras mutations in sporadic medullary thyroid carcinomas and activation of mTOR pathway., HIF and mTORC1 signalling seems active in both Basal cell carcinoma and trichoepithelioma., Comparative RNA-seq of adjacent sarcomatoid and clear cell histology of RCC indicates a proliferative phenotype and increased AURKA-dependent activation of mTOR signaling in sarcomatoid RCC, which could be targeted by available agents., 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)., Inhibition of mTOR signaling is a promising new strategy for improving treatment of EBV-associated T- and NK-cell lymphoma., Kv1.3 channels modulate human vascular smooth muscle cells proliferation independently of mTOR signaling pathway., By inducing autophagy via the ERK/AKT-mTOR-STAT3-Notch signaling cascade., 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, Targeting mTORC1 in combination with ALK leads to enhanced antitumor efficacy and prolongs survival in mouse xenograft models of human neuroblastoma coexpressing ALKF1174L and MYCN., Alteration of the mTOR pathway and LOH of the tuberous sclerosis complex genes is a frequent pathogenesis in hepatic AMLs., Activated mTORC1 elicits IL8 gene expression via the activation of an IRE1-JNK signalling cascade., MLN0128 is an effective inhibitor of MTOR, inhibiting both mTORC1 and mTORC2 activity., may be one of the key target molecules for the prevention of secondary bacterial infection caused by primary virus infection, Abnormal dendritic patterning in tuberous sclerosis is not dependent on mTOR but is dependent on ERK1/2 pathway., miRNA mediated alterations in mTOR and ERalpha signaling establishes a new mechanism for altered estrogen responses independent of growth factor stimulation., the regulation of YAP by mTOR and autophagy is a novel mechanism of growth control, matching YAP activity with nutrient availability under growth-permissive conditions., Evidence show that mTOR-mediated phosphorylation of SENP3 facilitates the interaction with NPM1, thereby promoting nucleolar targeting., Suppressed the mTOR-HIF pathway., Authors identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins., Data show that the induction of resveratrol-dependent autophagy is mediated via the mechanistic target of Akt proto-oncogene protein/rapamycin complex 1 (mTORC1)/S6 kinase 1 (S6K1) signaling pathway., regulatory relationship between mTOR and the MondoA-TXNIP axis that we propose contributes to glucose homeostasis, SKLB-M8 inhibited melanoma tumor growth by inducing apoptosis through the AKT/mTOR signaling pathway., The positive rates of mTOR, eIF4E and 4EBPs in patients with lymph node metastasis were significantly higher than in patients without lymph node metastasis., The growth inhibitory potential of bovine lactoferrin was mainly dependent on cell cycle arrest and not on induction of cell death by apoptosis. This effect was associated with downregulation of phosphorylation and total levels of mTOR., PKC-delta activates p38/MAPK, responsible for the inhibition of MMP-2 and -9 secretion, PKC-epsilon activates a pathway made of ERK1/2, mTOR and S6K responsible for the inhibition of NHE1 activity and cell migration., Results suggest that Mst1 regulates proliferation of glioma cells via AKT/mTOR signaling pathway, rapamycin, a MTOR inhibitor and autophagy inducer, could reduce total and phospho-KIT expression levels and enhance apoptosis in imatinib-resistant GIST cells, IGF-1 could promote proliferation and osteogenic differentiation of DPSCs via mTOR pathways, which might have clinical implications for osteoporosis., Leptin induced GRP78 expression through the PI3K-mTOR pathway in neuronal cells., Data show that the serine/threonine-protein kinase mTOR inhibitor everolimus as potential new treatment option for head and neck squamous cell carcinomas., Functional variants in DPYSL2 sequence increase risk of schizophrenia and suggest a link to mTOR signaling, IL-1b, which normally bridges innate and adaptive immunity, induces the production of the major haematopoietic/proleukaemic growth factor SCF through the PI-3K/mTOR pathway and the HIF-1a transcription complex., The activity of wedelolactone on osteoclasts and breast cancer-mediated osteoclastogenesis was associated with the inhibition of Akt/mammalian target of the rapamycin signaling pathway (mTOR)., Re-expression of miR-149 significantly inhibited HCC cell proliferation and tumorigenicity by regulating AKT1/mTOR pathway., The activation of mTOR is required for the pro-inflammatory response via NF-kappaB-dependent pathway in human monocytes., using specific inhibitors, we found that the activation of EGFR signaling promoted GBM growth through PI3k/Akt/mTor signaling pathways., overexpressed in ileal neuroendocrine tumors, Data indicate that AZD-2014 disrupts mTORC1/2 assembly/activation, downregulating mTOR-regulated genes., 25(OH)2D3-induced expression of TREM-1 was inhibited by rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, indicating the involvement of mTOR., Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption., these results suggest that breast cancer cells may rely on mTORC2-Chk1 pathway for survival, certain Akt/mTOR/4E-BP1 pathway signals could be novel therapeutic targets for Merkel cell carcinomas regardless of Merkel cell polyomavirus infection status, These results indicate that protein ingestion causes insulin resistance and the insulin-desensitizing effect of protein ingestion is not due to inhibition of AKT by leucine-mediated mTOR signaling., these data collectively indicate that activation of mTOR signaling is required for the robust functions of Tem cells in humans and suggest that defective mTOR signaling in Temra contributes to their functional impairment., In TSC2-deficient angiomyolipoma patient cells, IRF7 is a pivotal factor in the Rheb/mTOR pathway., Concurrent inhibition of tumor cells and activated stromal cells by a PDGF-R tyrosine kinase inhibitor and an mTOR inhibitor used in combination may represent a novel therapeutic approach for colorectal cancer, mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma., the role of PLC and PI3K/Akt/mTOR signal transduction pathways in pathophysiology., 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., 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, identify autophagy as a novel activator of MTORC2 signaling leading to connective tissue growth factor induction and myofibroblast differentiation, 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., This study demonstrated that the mTOR pathway has been related to extrapyramidal symptoms susceptibility and Antipsychotic response., Azithromycin and to a lesser extent clarithromycin act as immunosuppressive agents on CD4+ T-cells by inhibiting mTOR activity., Through the inhibition of AKT/ NF-kappaB/ mTOR signaling pathway., Osteosarcoma cell lines are responsive to pharmacologic and genetic inhibition of the PI3K/mTOR pathway both in vitro and in vivo, functional studies reveal that the Akt-mTOR signaling pathway, a major negative regulator of autophagy, is inhibited by oxamate., Data suggest that a combined pharmacologic inhibition of mTORC1 and Mnk1/2 kinases offers a therapeutic opportunity in blast crisis-chronic myeloid leukemia (BC-CML)., Supporting this idea, we identified a downstream target of the TGFb-miR-96 signaling pathway to be AKT1S1 mRNA, whose translated protein is a negative regulator of mTOR kinase., conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression, Findings establish that the convergence of 2 distinct Ras effector pathways on mammalian target of rapamycin signaling maintains neurofibromatosis type 1 mouse optic glioma growth., Collectively, Trichomonas vaginalis GP63 metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite., mTORC1 is significantly reduced in the brains of Huntington's disease patients., SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR, Glut3 is a downstream target of mTORC1, and it is critical for oncogenic mTORC1-mediated aerobic glycolysis and tumorigenesis., The results of this study suggested that dysregulation of mTORC1 signaling has an important role in the pathogenesis of a subgroup of nonsyndromic autism spectrum disorders., Cardiac fibrosis and hypertrophy were induced by NOX4 by activation of the Akt/mTOR pathway., pS6 expression is associated with the characteristics of a high Ki-67 subset in ER+ and HER2- breast cancer whose proliferation seemed to be affected by activation possibly of the mTOR/S6 pathway., 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., This study demonstrated down-regulation of the Akt/mTOR pathway, specifically via p70S6K/eIF4B, in idiopathic autism., Plumbagin promotes cell cycle arrest and autophagy but inhibits epithelial to mesenchymal transition phenotype in pancreatic cancer cells with the involvement of PI3K/protein kinase B/mTOR/p38 MAPK mediated pathways., Alisertib cell cycle arrest and promotes autophagic cell death but inhibits EMT in pancreatic cancer cells with the involvement of PI3K/Akt/mTOR, p38 MAPK, Erk1/2, and Sirt1-mediated signaling pathways., Dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 synergizes with chloroquine to induce apoptosis in embryonal rhabdomyosarcoma., Abeta species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis, Overview of the mTOR signaling pathway and the mechanisms of mTOR in autophagy regulation. [Review], Taken together, these findings reveal an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of hepatocarcinoma cells and suggest NAMPT inhibition as a potential treatment option for HCC., Tanshinone IIA inhibits HIF-1alpha and VEGF expression in breast cancer cells via mTOR/p70S6K/RPS6/4E-BP1 signaling pathway., Everolimus inhibited mTOR in tested cell lines by decreasing S6 phosphorylation, mediating its anti-proliferative effect by G0/G1 cell cycle arrest and induction of apoptosis., Tumor suppressor function of LZTS1 in colorectal carcinoma is mainly mediated by the AKT-mTOR pathway., statistically significant association was found between mTOR/p-mTOR expression and NSCLC patients' prognosis, the main evidence from animal and human studies supporting the hypothesis that mTOR may be a novel pharmacological target for the management of chronic pain., Maximal activation of selective autophagy during stress is attained by the ability of Huntingtin to bind ULK1, a kinase that initiates autophagy, which releases ULK1 from negative regulation by mTOR., our findings indicate that PI3K inhibitors may be ineffective in some lapatinib-resistant HER2+ breast cancers with PI3K-independent activation of mTOR kinase, which may instead benefit from mTOR or Hsp90 inhibitors, activation of the Akt/mTOR pathway by exercise training impaired in the skeletal muscle of hypoxemic patients with COPD, DJ-1 protein may be involved in endometrial cells proliferation, migration and angiogenesis by modulating the PI3K/Akt/p-mTOR signaling pathway, which provides an underlying theoretical target for endometriosis and adenomyosis, results of this study showed that AKT1 and mTOR in the pathophysiology of Bipolar disorder and support the relevance of blood mRNA expression., The schweinfurthin class of compounds as a novel approach to modulate oncogenic mTOR/AKT signaling for cancer treatment., it is also becoming evident that mTOR signaling, which regulates an array of anabolic processes, including ribosome biogenesis, is often exploited by cancer cells to sustain proliferation through the upregulation of global protein synthesis., The p-p70S6K, p-Gli1, p-mTOR, and p-AKT protein expression were inhibited., Studies indicate that mammalian target of rapamycin (mTOR) pathway is a major therapeutic target in the treatment of hematological malignancies., miR-491-3p/mTORC2/FOXO1 has a role in tongue cancer response to chemotherapy, mTOR is activated after imatinib secondary resistance in gastrointestinal stromal tumors., GCN2 activation and phosphorylation of eIF2alpha in response to mTORC1 inhibition are necessary for autophagy., mTORC1 regulates cell adhesion through S6K1 and 4E-BP1 pathways, but mTORC2 regulates cell adhesion via Akt-independent mechanism, Nuclear p-mTOR expression can be used as a prognostic indicator predictive of DFS and OS in advanced OSCC patients with ENE, Che-1 controls mTOR through the induction of Redd1 and Deptor, two important repressors of mTOR., indicate mTOR-related genes harbored not only somatic mutations but also mutational intratumoral heterogeneity and loss of expression, which together might play a role in tumorigenesis of colorectal cancers, The results suggest that the functional rs2295080 T>G in the promoter of MTOR may influence the susceptibility of CRC in the Chinese population through regulating the transcription activity of MTOR promoter., Sorafenib appears to inhibit hepatic tumor growth by downregulating PI3k/Akt/mTOR signaling pathway., An imbalance was found between mTORC1 and mTORC2 activity in the cerebellum of transgenic Angelman syndrome mice., These results have implicated that mTor is involved in regulating tau distribution in subcellular organelles and in the initiation of tau secretion from cells to extracellular space., Letter/Case Report, brain somatic activating mutations in MTOR cause focal cortical dysplasia type II, Tumor cells can quickly adapt to genotoxic conditions via mTOR-mediated reprogramming., Nedd4 promoted autophagy and was associated with the mTOR signalling pathway., CRNDE, a long-noncoding RNA, promotes glioma cell growth and invasion through mTOR signaling pathway., mTOR mutation is associated with breast cancer., Structural alterations induced by hyperactivated mTOR signaling are critical for epileptogenesis, newer evidence suggests that mTOR activation on its own may enhance neuronal excitability., conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy, MTOR mammalian target of rapamycin SNP single nucleotide polymorphism qRT-PCR quantitative real-time polymerase chain reaction URSA unexplained recurrent spontaneous abortion mTORC1 mTOR complex 1 ESC embryonic stem cells, upon antigen recognition, mTORhi CD4+ T cells are destined to become highly glycolytic effector cells., EtOH partially inhibits mTOR signaling and protein translation, compared to INK128's complete mTOR inhibition., Increase of microRNA-210, decrease of raptor gene expression and alteration of mammalian target of rapamycin regulated proteins following mithramycin treatment of human erythroid cells., A germline MTOR mutation in Aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces., These results indicate that metformin can suppress the proliferation, migration, and EMT of thyroid cancer cell lines by inhibiting mTOR signaling., MiR-199a-3p in glioma cell lines has effects similar to the tumor suppressor gene on cellular proliferation via the AKT/mTOR signaling pathway., Data suggest that the antitumor activity of CC-223 was mediated through inhibition of both mTOR kinase complexes mTORC1 and mTORC2., The applied drugs showed remarkable suppression of mTOR expression, which might delay tumor progression., Our findings support the de-regulation of the PI3K/Akt/mTOR and MAPK signaling pathways in type I endometrial carcinomas suggesting involvement of these pivotal pathways in endometrial carcinogenesis, rs2059806 of INSR was associated with both type 2 diabetes mellitus and type 2 diabetic nephropathy, while rs7212142 of mTOR was associated with type 2 diabetic nephropathy but not type 2 diabetes mellitus in a Chinese Han population., mTORC2 regulates lipopolysaccharides-induced expression of IL-12 and IL-23 in human dendritic cells., Report the novel finding of an MTOR mutation associated with nonsyndromic cortical dysplasia. Somatic-specific mutations in MTOR should be considered in patients with hemispheric malformations and more restricted forms of cortical dysplasia., significant and consistent inhibition of the mTOR pathway (using S6RP as the readout) was observed in patients treated with everolimus, mitotic cap-dependent translation is generally sustained during mitosis by CDK1 phosphorylation of 4E-BP1 even under conditions of reduced mTOR signaling, mTOR activity is not required for cone survival, over the period of one year in mouse suggesting that trophic support for cones downstream of PI3K is independent of mTOR signaling., A new dimension in mTOR-rictor relationship., Collybistin forms a complex with mTOR and eIF3 and by sequestering these proteins downregulates mTORC1 signaling and protein synthesis potentially contributing to intellectual disability and autism., that cilia and autophagy regulate reciprocally through the MTOR signaling pathway and ubiquitin-proteasome system, 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., mTOR complex 2 regulates cell survival and growth in non-small-cell lung cancer (NSCLC) cell lines by stabilizing Mcl1., Report combination of ruxolitinib and PI3K/mTOR inhibitors provokes a significant pro-apoptotic effect in JAK2V617F mutated tumor cells., Data indicate that phosphatidic acid (PA) specifically disrupts DEPTOR-mTORC1 interaction., LARP1 is a target of mTORC1 that associates with TOP mRNAs via their 5'TOP motif to repress their translation., Results show that phosphorylated mTOR was specifically overexpressed in the analyzed malignant pleural mesothelioma samples., This review focuses on biochemical mechanisms involving enzymes--specifically, mTOR, AMPK, and Sirt1--that are currently considered important for these adaptive responses, providing an overview of the interactions of the main players in this process., 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, Data suggest that amino acid transporter SLC38A9 controls mTORC1 activity through binding to the Rag-Ragulator complex at the lysosome upon amino acid availability., pUL38 can activate mTORC1 in both TSC2-dependent and -independent manners., Significantly down-regulates the activity of the PI3K/AKT/mTOR signaling pathway., Data suggest that G6PT (glucose-6-phosphate transporter) modulates autophagy independent of its transport activity; G6PT appears to up-regulate autophagy via inactivation of mTORC1; knockdown of G6PT expression activates mTORC1 activity., placental level may correlate with early catch-up growth following intrauterine growth restriction, data reveal that HSF1 can be activated by glucose-mTOR pathway in hepatocellular carcinoma., HER2-mTOR signaling-driven breast cancer cells require ER-associated degradation to survive., MTOR mutations were identified in individuals with focal cortical dyplasia type IIb., investigated the involvement of the RAS/MEK/ERK and PI3K/AKT/mammalian target of rapamycin (mTOR) pathways on metabolic alteration in lung adenocarcinoma cell lines with activating EGFR mutations, Our results show the complexity of determining causal genetic alterations that can predict responsiveness to mTOR inhibition., This result indicates that p-mTOR might play a more pivotal role in the biologic behavior of early small cell lung cancers than advanced ones, MUC16 knockdown leads to inhibition of mTOR activity and reduced expression of its downstream target c-MYC, a key player in cellular growth, proliferation and metabolism., Dienogest treatment of endometriotic cells suppresses AKT and ERK1/2 activity, thereby in turn inhibiting mTOR, inducing autophagy, and promoting apoptosis., Data suugest that S-phase kinase-associated protein 2 (Skp2)-mediated Ras-related GTP-binding protein RagA ubiquitination recruits GATOR1 to restrict mTORC1 signaling upon sustained amino acid stimulation., Inhibition of mTOR signaling ameliorates vascular calcification via Klotho upregulation., Data indicate that the reduction of hypoxia-inducible factor-1alpha (HIF-1alpha) expression observed was positively correlated with phospho-mTOR protein reduction., Data indicate that the mTOR serine-threonine kinase (mTOR)-dependent immune-metabolic network leading to long-term immune-modulation and might have relevance for novel therapeutic settings in kidney transplants., In colorectal cancer, MTOR expression was higher in cancer tissues than in adjacent tissue. Lymph node metastasis was related to MTOR expression., SNP rs2536 of mTOR gene may be associated with the risk of pediatric epilepsy, Our data show that combined targeting of MEK and PI3K-AKT with mTOR is a better option than single agents alone for KRAS mutant NSCLC, thus opening the possibility of a beneficial treatment strategy in the future., tubulation requires mTOR activity, and we identified two direct mTOR phosphorylation sites on UVRAG (S550 and S571) that activate VPS34., MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation., Data show that interferon-gamma regulated the metabolism and mRNA translation of macrophages by targeting the kinases mTORC1 and MNK1/2, both of which converge on the selective regulator of translation initiation eukaryotic initiation factor-4E (eIF4E)., Data show that immunoglobulin-like transcript 4 (ILT4) increases the expression of the co-inhibitory molecule B7-H3 through PI3K/AKT/mTOR signalling., Data show that hypoxia-inducible factor 1, alpha subunit (HIF-1alpha) is activated via an proto-oncogene protein Akt/mTOR protein signaling pathway in LCC2 and LCC9 breast cancer cells., Akt/mTORC1 signaling and glucose metabolism is inhibited by halofuginone treatment of colorectal cancer, In inhibiting the tumorigenesis through targeting the mTOR/p- 4E-BP1/p-S6K1 pathway., Data show that leucine alone stimulates mTORC1 signaling and ribosomal protein s6 kinase 1 (S6K1) phosphorylation., glucose-dependent acetylation of Rictor, a central component of mechanistic target of rapamycin complex 2 (mTORC2), promotes tumor growth and resistance to epidermal growth factor receptor (EGFR)-, PI3K-, and AKT-targeted therapies, Temozolomide in combination with NVP-BEZ235 act synergistically to inhibit proliferation of glioma cells by down-regulating of the PI3K-AKT-mTOR pathway., Glycyrrhizic acid inhibits leukemia cell growth/migration by blocking AKT/mTOR/STAT3 signaling., Rapamycin induced growth inhibition of human retinoblastoma cells, and inactive of mTOR pathway and downregulation of Bmi-1 was involved in its action mechanism., target of rapamycin (TOR), a nutrient-sensitive protein kinase that negatively regulates autophagy, directly targets and inactivates the TRPML1 channel and thereby functional autophagy, through phosphorylation., Data suggest that utilising a lower dose of cisplatin combined with mTOR inhibition is a viable treatment option and addresses the challenge of cisplatin dose-dependent toxicity in cervical cancer., role in platelet cell differentiation, Collectively, these results highlight the cleavage of shp-1 as a critical event in reprogramming LPS pathway to promote both neutrophil recruitment and survival and provide a novel mechanistic framework for the investigation of the post-traumatic MODS., Tamoxifen stimulates the mTOR-pathway in breast tumor stem cells, but this can be antagonized using mTOR-inhibitors., Data show that both AMPKalpha cleavage and MMP9 expression are required for Toll-like receptor 4 (TLR4)-mediated mTORC1 activation and HIF-1alpha expression., Inactivated Sendai virus induces apoptosis and autophagy via the PI3K/Akt/mTOR/p70S6K pathway in human non-small cell lung cancer cells., MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1., Data indicate that forkhead box P3 protein (FOXP3) invariant NKT (iNKT) cells only acquired suppressive abilities when cultured in the presence of the mechanistic target of rapamycin (mTOR) inhibitor rapamycin., Increased activity of mTOR in obesity may compensate for the negative consequences of overnutrition, whereas dysregulation of mTOR may lead to abnormal lipid partitioning and metabolic disease--{review}, Studies suggest that mechanistic target of rapamycin protein (mTOR) could regulate ATP and Acetyl-CoA synthesis in mitochondria with post translational regulation, usually phosphorylation., Case Report, cyclic stretch regulates energy metabolism in MG63 cells partially through the Akt/mTOR/p70s6k signaling pathway., Data suggests that point mutations in the mTOR pathway may lead to downstream mTOR hyperactivation through multiple different mechanisms to confer a proliferative advantage to a tumor cell., Inhibition of snail expression and quercetin suppressive renal carcinoma by altering AKT/mTOR/ERK1/2 signaling pathways., Phospho-mTOR overexpression is abundant in colorectal carcinoma and linked to left-sided tumor localization., PI3K/AKT/mTOR pathway activation is associated with higher invasive and migratory capacities in subpopulations of human ovarian cancer cell lines., Microarray and Proteomic Analyses of Myeloproliferative Neoplasms with a Highlight on the mTOR Signaling Pathway., mTOR controls the senescence-associated secretory phenotype by differentially regulating the translation of the MK2 (also known as MAPKAPK2)., It plays a role in cell survival, cell differentiation and cell proliferation in neoplasms., Data suggest that combination of proto-oncogene protein B-raf (BRAF) and mTOR serine-threonine kinase (mTOR) inhibition forms the basis of a treatment regimen of thyroid cancer., rs1034528 CG/CC and rs3806317 GA/GG variant genotypes were associated with an increased risk of gastric cancer under a dominant model, NAT12/NAA30 plays an important role in growth and survival of glioblastoma-initiating cells possibly by regulating hypoxia response (HIF1a), levels of p-MTOR (Ser2448) and the p53 pathway., Endothelial mTORC2 regulates angiogenesis, in part by regulation of endothelial cell FAK activity, matrix adhesion, and cytoskeletal remodeling, independent of Akt/mTORC1., the presence of a Fyn-induced endoplasmic reticulum stress that occurred, at least in part, through the activation of mTORC1, as well as subsequent activation of the IRE1alpha-JNK pathway driving cell death, Rab1A-dependent activation of mTORC1 has as role in amino acid signaling promotes growth and metastasis of hepatocellular carcinomas, Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells., MTOR rs1064261 was associated with increased risk of GC in men., RGS10 suppression increases Rheb-GTP and mTOR signaling in ovarian cancer cells., RY-2f, an isoflavone analog, overcomes cisplatin resistance to inhibit ovarian tumorigenesis via targeting the PI3K/AKT/mTOR signaling pathway., Studies indicate that the mTOR (mechanistic target of rapamycin) signalling pathway serves as the central regulator of cell metabolism and proliferation., these data suggest that DHA-induced apoptosis and autophagy in non-small cell lung cancer cells are associated with AMPK activation and PI3K/Akt inhibition, which in turn lead to suppression of mTOR, Role of mTOR in glioblastoma, Data show that both VEGF/VEGFR and mTOR inhibitors indicated antitumour activity following PD-1/PD-L1 blockade., MTOR-low or PTEN-high patients had better 3-year rates of OS., Data show that mTOR serine-threonine kinase (mTOR) inhibitor AZD2014 has broad antiproliferative effects across multiple cell lines., 4E-BP1 and p53 gene expressions were increased, but p-4E-BP1 and p-mTOR protein expressions were decreased in nsclc., These results indicate that the inhibitory effect of rapamycin may be due mainly to increased p14, p15, and p57 expression via promoter demethylation and decreased mTOR and p70S6K expression in ALL cell lines., mTOR in health and in sickness, Studies indicate the role of mammalian target of rapamycin (mTOR) in controlling and shaping the effector responses of innate immune cells., mitochondrial, purinergic, and mTOR signaling regulates neutrophil chemotaxis, mTOR inhibitor, sirolimus, suppresses the tumor's growth, suggesting that mTOR inhibitors might be effective in control of FLCN-deficient RCC., Studies indicate that rhe mammalian target of rapamycin (mTOR), a master regulator of protein synthesis, is shown to control the senescence-associated secretory phenotype by modulating gene transcription and mRNA translation and stabilization., In a study to reverse Corticosteroid resistance with rapamycin in COPD patients it was found that mTORC1/S6K activity is increased in COPD patients, and correlates with corticosteroid insensitivity., PI3K/AKT/mTOR pathway inhibitors in combination with autophagy inhibitors lead to further apoptosis in breast cancer cells., Results suggest that blocking both the mTOR kinase downstream targets 4E-BP1 protein and p70 S6 kinase 1, but not p70 S6 kinase 1 alone, prevents the migration of retinal pigment epithelium (RPE) cells., The increase of the canonical pathway of mTOR regulation., Our data thus show that mTOR acquires transforming activity through genetic changes in cancer, Data demonstrate that respiratory syncytial virus (RSV) is activating mTOR directly in CD8 T cells, indicating a role for mTOR during the course of RSV infection, Data suggest that nitroxoline induces anticancer activity through AMP-activated kinase (AMPK)/mTOR serine-threonine kinase (mTOR) signaling pathway via checkpoint kinase 2 (Chk2) activation., Our results identify OspB as a regulator of mTORC1 and mTORC1-dependent cell proliferation early during S. flexneri infection and establish a role for IQGAP1 in mTORC1 signaling, These data highlight the central role of REDD1 in regulating both protein synthesis and autophagy in skeletal muscle during sepsis., 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 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 that the combination with the HER-2 proto-oncogene protein (HER2) inhibitor lapatinib and the inhibition of mTOR serine-threonine kinase (mTor) affords the highest degree of synergy., Propofol inhibited tumor size, cell viability and promoted cell apoptosis via inhibiting mTOR/p70S6K pathway mediated by HOTAIR in cervical cancer., the combination of an mTOR inhibitor and an autophagy inhibitor may be effective in the treatment of osteosarcoma because it effectively induces the apoptotic pathway., SR4 Uncouples Mitochondrial Oxidative Phosphorylation, Modulates AMP-dependent Kinase (AMPK)-Mammalian Target of Rapamycin (mTOR) Signaling, and Inhibits Proliferation of HepG2 Hepatocarcinoma Cells., show that mTOR inhibitor rapamycin and ACSL4 inhibitor rosiglitazone can act in combination to inhibit cell growth, Protein tyrosine phosphatase nonreceptor type 12 suppresses the proliferation of renal cell carcinoma by inhibiting the activity of the PI3K/mTOR pathway., MTOR p.E1799K mutation can now be classified as a pathogenic gain-of-function mutation that causes megalencephaly and cognitive impairment in humans., Data show that Ba/F3 cells transformed with mutant HRAS protien indicated equal sensitivity towards Map kinase kinase (MEK) and mTOR serine-threonine kinase (mTOR) inhibition., our findings provide for the first time that PF-04691502 inhibits the constitutively activated PI3K/mTOR pathway in aggressive B-cell NHL cell lines associated with inhibition of cell cycle progression, cell proliferation and promotion of apoptosis., Specific mTOR pathway genes are potentially important to breast cancer risk and to the ER negativity in African American women., Our data show for the first time that nutrient starvation conditions activate mTORC1 and increase radiosensitivity through mTORC1 activation in liver cancer cell lines, HepG2 and HuH6., Study provides further evidence for the role of mTOR hyperactivation and reduced autophagy in the accumulation of protein oxidative damage during Down's Syndrome, The SLC7A5 knockout cells phenocopies YAP/TAZ knockout cells which exhibit defective mTORC1 activation in response to amino acids., TMP21 modulates cell growth in papillary thyroid cancer cells by inducing autophagy, which may be associated with activation of AMPK/mTOR pathway., Akt/mTOR signaling was hyperactive in low miR-149 expressing gliomas., Our results suggest that silencing of AT1R inhibits EMT induced by HG in HK-2 cells via inactivation of mTOR/p70S6K signaling pathway., Expression of MMP2 and MMP7 in gastric cancer is not associated with mTOR, MMP9 expression might be related to mTOR signalling in a subset of tumors, Data show that voltage-dependent anion channel 1 (VDAC1) knockout cells are resistant to AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) modulation by itraconazole, indicating VDAC1 is the mediator of the activity., Data indicate that inhibiting protein kinase mammalian target of rapamycin (mTOR) stimulates both autophagy and proteasome-mediated proteolysis., To our knowledge, this is also the first report to provide a rationale for the implication of cross-linking between Nrf2 and mTOR signaling., mTOR regulates the nutritional support of spermatogenesis by Sertoli cells and redox balance in these cells., Torin2, an ATP competitive mTOR inhibitor, inhibits cell growth of adult T-cell leukemia/lymphoma cell lines in a concentration-dependent manner., rapamycin reduces mTOR phosphorylation and subsequently inhibit NF-kappaB activation and suppresses LOX-1, resulting in a reduction in ox-LDL uptake in HUVECs, mTOR plays a key role in the initiation and development of breast cancer., Hereditary skin diseases showed MTOR protein genetic mutation., Mefloquine acts on gastric cancer cells via suppressing PI3K/Akt/mTOR pathway., Data suggest MTMR3 has multiple functions in regulation of autophagy; one mechanism appears to be direct interaction between MTMR3 and mTORC1 (MTOR, mLST8, raptor) which inhibits phosphorylation activity of mTORC1; MTMR3 is localized to Golgi apparatus., 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., This study report that protein levels of the MTOR was increased in Progressive Supranuclear Palsy and Corticobasal Degeneration brains., It was concluded that over-activation of the mTORC1/4E-BP1/p21 pathway is a frequent and clinically relevant alteration in head and neck squamous cell carcinomas., These results suggest that Porphyromonas gingivalis outer membrane vesicles outer membrane vesicles., Hydrogen sulfide promotes angiogenesis by downregulating miR-640 and increasing the levels of HIF1A through the VEGFR2-mTOR pathway., expression of Akt and mTOR protein was enhanced in the endurance exercise group, whereas only the level of mTOR was elevated following Resistance training., direct connection between the cellular PI3K/AKT/mTOR signaling pathway, frequently activated in human hepatocarcinogenesis, and the enrichment of oncogenic transcription factors of the FBP family, rapamysin, a suppressor of mTOR, causes completely different effects on tumor associated macrophages and cells of microglia., Our study demonstrates that the IGF1R/p110b/AKT/mTOR axis confers resistance to BYL719 in PIK3CA mutant breast cancers., Activation of the PI3K/mTOR Pathway following PARP Inhibition in Small Cell Lung Cancer., MTORi use was associated with an increased risk of AG., Ammonia induced autophagy by MTOR is mediated by DRD3., miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR-p-PI3K/AKT-c-JUN.,
OMIM_DISEASE Smith-Kingsmore syndrome,
SP_COMMENT function:Acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Part of the TORC2 complex which plays a critical role in AKT1 Ser-473 phosphorylation, and may modulate the phosphorylation of PKCA and regulate actin cytoskeleton organization., similarity:Belongs to the PI3/PI4-kinase family., similarity:Contains 1 FAT domain., similarity:Contains 1 FATC domain., similarity:Contains 1 PI3K/PI4K domain., similarity:Contains 7 HEAT repeats., subunit:Interacts with the FKBP12-rapamycin complex. Binds UBQLN1. Forms part of the mammalian target of rapamycin 2 complex (TORC2) comprised of FRAP1, GBL, PRR5, RICTOR and SIN. TORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to PRR5 and RICTOR within the TORC2 complex., tissue specificity:Expressed in numerous tissues, with highest levels in testis.,