Gene Symbol: p110
Description: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
Alias: CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, PI3K-alpha, p110-alpha, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, PI3-kinase p110 subunit alpha, phosphatidylinositol 3-kinase, catalytic, 110-KD, alpha, phosphatidylinositol 3-kinase, catalytic, alpha polypeptide, phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, alpha isoform, phosphoinositide-3-kinase, catalytic, alpha polypeptide, ptdIns-3-kinase subunit p110-alpha, serine/threonine protein kinase PIK3CA
Species: human
Products:     p110

Top Publications

  1. Kadota M, Sato M, Duncan B, Ooshima A, Yang H, Diaz Meyer N, et al. Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA. Cancer Res. 2009;69:7357-65 pubmed publisher
    ..Our gene amplification and somatic mutation analysis of breast primary tumors provides a coherent picture of genetic events, both corroborating and novel, offering insight into the genetic underpinnings of breast cancer progression. ..
  2. Suda T, Hama T, Kondo S, Yuza Y, Yoshikawa M, Urashima M, et al. Copy number amplification of the PIK3CA gene is associated with poor prognosis in non-lymph node metastatic head and neck squamous cell carcinoma. BMC Cancer. 2012;12:416 pubmed publisher
    ..026) Copy number amplification of the PIK3CA gene is associated with poor prognosis in HNSCC patients without lymph node metastasis. The PIK3CA copy number status will serve as a marker of poor prognosis in patients with HNSCC. ..
  3. Lindhurst M, Parker V, Payne F, Sapp J, Rudge S, Harris J, et al. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nat Genet. 2012;44:928-33 pubmed publisher
    The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism...
  4. Coffee E, Faber A, Roper J, Sinnamon M, Goel G, Keung L, et al. Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer. Clin Cancer Res. 2013;19:2688-98 pubmed publisher
    ..We examined phosphoinositide 3-kinase (PI3K)/mTOR signaling in BRAF(V600E) CRC cell lines after BRAF inhibition and cell viability and apoptosis after combined ..
  5. Engelman J, Chen L, Tan X, Crosby K, Guimaraes A, Upadhyay R, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med. 2008;14:1351-6 pubmed publisher
    Somatic mutations that activate phosphoinositide 3-kinase (PI3K) have been identified in the p110-alpha catalytic subunit (encoded by PIK3CA)...
  6. Kuhn E, Wu R, Guan B, Wu G, Zhang J, Wang Y, et al. Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses. J Natl Cancer Inst. 2012;104:1503-13 pubmed publisher
    ..Molecular genetic aberrations involving the p53, cyclin E-FBXW7, and PI3K pathways represent major mechanisms in the development of uterine serous carcinoma.
  7. Rudd M, Price J, Fogoros S, Godwin A, Sgroi D, Merino M, et al. A unique spectrum of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas. Clin Cancer Res. 2011;17:1331-40 pubmed publisher
    ..The exons 1-7 mutations localized to the ABD, ABD-RBD linker and C2 domains of p110α...
  8. Liu P, Cheng H, Santiago S, Raeder M, Zhang F, Isabella A, et al. Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms. Nat Med. 2011;17:1116-20 pubmed publisher
    ..gain-of-function mutations are a common oncogenic event in human malignancy, making phosphatidylinositol 3-kinase (PI3K) a target for cancer therapy...
  9. Shull A, Latham Schwark A, Ramasamy P, Leskoske K, Oroian D, Birtwistle M, et al. Novel somatic mutations to PI3K pathway genes in metastatic melanoma. PLoS ONE. 2012;7:e43369 pubmed publisher
    ..We hypothesized that somatic mutations in the Phosphoinositide 3-Kinase (PI3K) pathway, which promotes proliferation and survival, may coincide with BRAF(V600) mutations and contribute to ..

More Information

Publications285 found, 100 shown here

  1. Samuels Y, Waldman T. Oncogenic mutations of PIK3CA in human cancers. Curr Top Microbiol Immunol. 2010;347:21-41 pubmed publisher
    The involvement of the PIK3CA gene product p110α, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K), in human cancer has been suggested for over 15 years, and support for this proposal had been provided by both genetic and ..
  2. Loi S, Michiels S, Baselga J, Bartlett J, Singhal S, Sabine V, et al. PIK3CA genotype and a PIK3CA mutation-related gene signature and response to everolimus and letrozole in estrogen receptor positive breast cancer. PLoS ONE. 2013;8:e53292 pubmed publisher
    The phosphatidylinositol 3' kinase (PI3K) pathway is commonly activated in breast cancer and aberrations such as PI3K mutations are common...
  3. Tanaka H, Yoshida M, Tanimura H, Fujii T, Sakata K, Tachibana Y, et al. The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011;17:3272-81 pubmed publisher
    The phosphatidylinositol 3-kinase (PI3K) pathway plays a central role in cell proliferation and survival in human cancer...
  4. Bando H, Yoshino T, Shinozaki E, Nishina T, Yamazaki K, Yamaguchi K, et al. Simultaneous identification of 36 mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA in a single reaction by multiplex assay kit. BMC Cancer. 2013;13:405 pubmed publisher
    ..Moreover, mutations in KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA detected in Asian patients were not predictive of clinical benefits from cetuximab treatment, similar to the result obtained in European studies. ..
  5. Domingo E, Church D, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, et al. Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer. J Clin Oncol. 2013;31:4297-305 pubmed publisher
    ..Our findings are concordant with recent data and support the prospective investigation of adjuvant aspirin in PIK3CA-mutant CRC. ..
  6. Karapetis C, Jonker D, Daneshmand M, Hanson J, O Callaghan C, Marginean C, et al. PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer--results from NCIC CTG/AGITG CO.17. Clin Cancer Res. 2014;20:744-53 pubmed publisher
    ..Evaluation of predictive significance of BRAF mutations requires a larger sample size. ..
  7. Ogino S, Liao X, Imamura Y, Yamauchi M, McCleary N, Ng K, et al. Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial. J Natl Cancer Inst. 2013;105:1789-98 pubmed publisher
    Somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal ..
  8. Wang W, Xie Y, Zhou Z, Qin Z, Wu J, He J. PIK3CA hypomethylation plays a key role in activation of the PI3K/AKT pathway in esophageal cancer in Chinese patients. Acta Pharmacol Sin. 2013;34:1560-7 pubmed publisher
    ..b>P110? and pAKT expression levels were detected with Western blotting...
  9. Hou J, Jiang D, Zhang J, Gavine P, Xu S, Liu Y, et al. Frequency, characterization, and prognostic analysis of PIK3CA gene mutations in Chinese esophageal squamous cell carcinoma. Hum Pathol. 2014;45:352-8 pubmed publisher
    ..085) but not disease-free survival (P = .238), suggesting that PIK3CA gene status may be a favorable predictive marker in ESCC patients. ..
  10. Vora S, Juric D, Kim N, Mino Kenudson M, Huynh T, Costa C, et al. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors. Cancer Cell. 2014;26:136-49 pubmed publisher
    Activation of the phosphoinositide 3-kinase (PI3K) pathway occurs frequently in breast cancer. However, clinical results of single-agent PI3K inhibitors have been modest to date...
  11. Loibl S, von Minckwitz G, Schneeweiss A, Paepke S, Lehmann A, Rezai M, et al. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol. 2014;32:3212-20 pubmed publisher
    Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer, with mutations in PIK3CA being the most common...
  12. Rodriguez Viciana P, Warne P, Vanhaesebroeck B, Waterfield M, Downward J. Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation. EMBO J. 1996;15:2442-51 pubmed
    ..These data show that PI 3-kinase is regulated by a number of mechanisms, and that Ras contributes to the activation of this lipid kinase synergistically with tyrosine kinases. ..
  13. Aziz S, Davies M, Pick E, Zito C, Jilaveanu L, Camp R, et al. Phosphatidylinositol-3-kinase as a therapeutic target in melanoma. Clin Cancer Res. 2009;15:3029-36 pubmed publisher
    Phosphatidylinositol-3 kinases (PI3K) are critical for malignant cellular processes including growth, proliferation, and survival, and are targets of drugs in clinical development...
  14. Zhou F, Xue M, Qin D, Zhu X, Wang C, Zhu J, et al. HIV-1 Tat promotes Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6-induced angiogenesis and tumorigenesis by regulating PI3K/PTEN/AKT/GSK-3? signaling pathway. PLoS ONE. 2013;8:e53145 pubmed publisher
    ..Mechanistic studies indicated Tat activates PI3K and AKT, and inactivates PTEN and GSK-3? in vIL-6 expressing cells...
  15. Liedtke C, Cardone L, Tordai A, Yan K, Gomez H, Figureoa L, et al. PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer. Breast Cancer Res. 2008;10:R27 pubmed publisher
    ..In this study, PIK3CA mutation was associated with a decreased rate of node-positive disease, particularly among ER-positive tumors. ..
  16. Li H, Lu Y, An Y, Wang X, Zhao Q. KRAS, BRAF and PIK3CA mutations in human colorectal cancer: relationship with metastatic colorectal cancer. Oncol Rep. 2011;25:1691-7 pubmed publisher
    ..Notably, our data indicated that colorectal cancers with KRAS and PIK3CA bi-mutations are more likely to develop into liver metastasis. ..
  17. Burke J, Perisic O, Masson G, Vadas O, Williams R. Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110? (PIK3CA). Proc Natl Acad Sci U S A. 2012;109:15259-64 pubmed
    The p110? catalytic subunit (PIK3CA) is one of the most frequently mutated genes in cancer...
  18. Lai Y, Mau B, Cheng W, Chen H, Chiu H, Tzen C. PIK3CA exon 20 mutation is independently associated with a poor prognosis in breast cancer patients. Ann Surg Oncol. 2008;15:1064-9 pubmed publisher
    ..is an independent risk factor for poor prognosis in breast cancer patients, indicating that differences in patient numbers with PIK3CA exon 20 mutations in study and control arms should be avoided in clinical trials of PI3K inhibitors.
  19. Qiu W, Schönleben F, Li X, Ho D, Close L, Manolidis S, et al. PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res. 2006;12:1441-6 pubmed
    ..A specific kinase inhibitor to PIK3CA may potentially be an effective therapeutic reagent against HNSCC or pharyngeal cancer in particular. ..
  20. Lauring J, Cosgrove D, Fontana S, Gustin J, Konishi H, Abukhdeir A, et al. Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations. Oncogene. 2010;29:2337-45 pubmed publisher
    ..These results suggest that mutations in critical genes within the PI3-kinase (PI3K) pathway are not functionally equivalent, and that other cooperative genetic events may be necessary to achieve ..
  21. Luo J, Field S, Lee J, Engelman J, Cantley L. The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex. J Cell Biol. 2005;170:455-64 pubmed
    ..Surprisingly, monomeric p85 is preferentially localized to these foci compared with the p85-p110 dimer, and these foci are not sites of phosphatidylinositol-3,4,5-trisphosphate production...
  22. Prenen H, De Schutter J, Jacobs B, De Roock W, Biesmans B, Claes B, et al. PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer. Clin Cancer Res. 2009;15:3184-8 pubmed publisher
    ..e., the PI3K/PTEN/AKT pathway...
  23. Zhang X, Deng H, Zhao X, Su D, Chen X, Chen L, et al. RNA interference-mediated silencing of the phosphatidylinositol 3-kinase catalytic subunit attenuates growth of human ovarian cancer cells in vitroand in vivo. Oncology. 2009;77:22-32 pubmed publisher
    The phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in ovarian cancer cell survival and proliferation...
  24. Yamamoto S, Tsuda H, Takano M, Iwaya K, Tamai S, Matsubara O. PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma. J Pathol. 2011;225:189-94 pubmed publisher
    ..A specific kinase inhibitor to mutated PIK3CA may potentially be an effective therapeutic reagent against these carcinomas. ..
  25. Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med. 2012;367:1596-606 pubmed publisher
    ..synthase 2 (PTGS2) (also known as cyclooxygenase-2) by aspirin down-regulates phosphatidylinositol 3-kinase (PI3K) signaling activity...
  26. Gallia G, Rand V, Siu I, Eberhart C, James C, Marie S, et al. PIK3CA gene mutations in pediatric and adult glioblastoma multiforme. Mol Cancer Res. 2006;4:709-14 pubmed
    The phosphatidylinositol 3-kinases (PI3K) are a family of enzymes that relay important cellular growth control signals...
  27. Hafner C, Stoehr R, van Oers J, Zwarthoff E, Hofstaedter F, Landthaler M, et al. FGFR3 and PIK3CA mutations are involved in the molecular pathogenesis of solar lentigo. Br J Dermatol. 2009;160:546-51 pubmed publisher
    ..The occurrence of these mutations in both SL and SK suggests a common genetic basis. Our findings furthermore substantiate previous speculations that UV exposure may be a causative factor for FGFR3 and PIK3CA mutations in human skin. ..
  28. Li H, Zhu R, Wang L, Zhu T, Li Q, Chen Q, et al. PIK3CA mutations mostly begin to develop in ductal carcinoma of the breast. Exp Mol Pathol. 2010;88:150-5 pubmed publisher
    ..08%), tested by the Chi-square test (P=0.269). There was no significant association between PIK3CA mutations and HER2 expression status (P=0.294, Chi-square test). ..
  29. Chamberlain M, Berry T, Pastor M, Anderson D. The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteins. J Biol Chem. 2004;279:48607-14 pubmed
    ..Thus, the p85alpha protein may play a role in the down-regulation of activated receptors through its temporal control of the GTPase cycles of Rab5 and Rab4. ..
  30. Schönleben F, Qiu W, Ciau N, Ho D, Li X, Allendorf J, et al. PIK3CA mutations in intraductal papillary mucinous neoplasm/carcinoma of the pancreas. Clin Cancer Res. 2006;12:3851-5 pubmed
    ..This is the first report of PIK3CA mutation in pancreatic cancer. Our data provide evidence that the oncogenic properties of PIK3CA contribute to the tumorigenesis of IPMN/IPMC. ..
  31. Zhang H, Liu G, Dziubinski M, Yang Z, Ethier S, Wu G. Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary epithelial cells. Breast Cancer Res Treat. 2008;112:217-27 pubmed
    ..Finally, LY294002, a PI3K inhibitor, can effectively inhibit cell growth in cell lines with different PIK3CAs...
  32. Michelucci A, Di Cristofano C, Lami A, Collecchi P, Caligo A, Decarli N, et al. PIK3CA in breast carcinoma: a mutational analysis of sporadic and hereditary cases. Diagn Mol Pathol. 2009;18:200-5 pubmed publisher
    The PI3K-Akt cascade is a key signaling pathway involved in cell proliferation, survival, and growth. Activating PIK3CA mutations have been reported in breast carcinoma (BC)...
  33. Lee C, Liu Q, Tomkowicz B, Yi Y, Freedman B, Collman R. Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways. J Leukoc Biol. 2003;74:676-82 pubmed
    ..Targeting these cellular signaling pathways may have benefit in controlling inflammatory sequelae of HIV infection such as in neurological disease. ..
  34. Rivière J, Mirzaa G, O Roak B, Beddaoui M, Alcantara D, Conway R, et al. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet. 2012;44:934-40 pubmed publisher
    ..identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway...
  35. Maeng C, Lee J, Van Hummelen P, Park S, Palescandolo E, Jang J, et al. High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide-3-kinase and BRAF mutations. PLoS ONE. 2012;7:e41655 pubmed publisher
    ..Our study led to the detection of potentially druggable mutations in esophageal SCC which may guide novel therapies in small subsets of esophageal cancer patients. ..
  36. Li X, Zhang Q, He W, Meng W, Yan J, Zhang L, et al. Low frequency of PIK3CA gene mutations in hepatocellular carcinoma in Chinese population. Pathol Oncol Res. 2012;18:57-60 pubmed publisher
    b>PI3K/AKT constitutes an important pathway regulating the signaling of multiple biological processes and plays a critical role in carcinogenesis. PIK3CA gene missense mutations have been reported in many human cancer types...
  37. Levine D, Bogomolniy F, Yee C, Lash A, Barakat R, Borgen P, et al. Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin Cancer Res. 2005;11:2875-8 pubmed
    Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, resulting in increased cell proliferation, survival, and motility, is believed to play an oncogenic role in many cancer types...
  38. Buttitta F, Felicioni L, Barassi F, Martella C, Paolizzi D, Fresu G, et al. PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma. J Pathol. 2006;208:350-5 pubmed
  39. Kasper M, Collins K. Nef-mediated disruption of HLA-A2 transport to the cell surface in T cells. J Virol. 2003;77:3041-9 pubmed
  40. Kim J, Chae Y, Sohn S, Kang B, Moon J, Lee S, et al. Clinical significance of genetic variations in the PI3K/PTEN/AKT/mTOR pathway in Korean patients with colorectal cancer. Oncology. 2010;79:278-82 pubmed publisher
    Signaling through the PI3K/PTEN/AKT/mTOR pathway is responsible for balancing cell survival and apoptosis...
  41. Kompier L, Lurkin I, van der Aa M, van Rhijn B, van der Kwast T, Zwarthoff E. FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy. PLoS ONE. 2010;5:e13821 pubmed publisher
    ..We showed that 88% of patients presenting with low-grade NMI-BC are eligible for such a follow-up. This may contribute to a reduction in the number of cystoscopical examinations. ..
  42. Konstantinova D, Kaneva R, Dimitrov R, Savov A, Ivanov S, Dyankova T, et al. Rare mutations in the PIK3CA gene contribute to aggressive endometrial cancer. DNA Cell Biol. 2010;29:65-70 pubmed publisher
    ..3%; p = 0.02). In all other comparisons exons 9 and 20 mutation distribution did not differ. These results suggest the need for further exploration of the significance of PIK3CA mutations in respect to aggressive EC. ..
  43. Fenic I, Steger K, Gruber C, Arens C, Woenckhaus J. Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell carcinoma. Oncol Rep. 2007;18:253-9 pubmed
    ..mutations in exons 9 and 20, the genomic gain and amplification of PIK3CA, the expression of PIK3CA mRNA and the p110 alpha protein, as well as the expression of phosphorylated-Akt (pAkt) in 33 cases of HNSCC and compared the results ..
  44. Catasus L, Gallardo A, Cuatrecasas M, Prat J. PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters. Mod Pathol. 2008;21:131-9 pubmed
  45. Barbi S, Cataldo I, de Manzoni G, Bersani S, Lamba S, Mattuzzi S, et al. The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type. J Exp Clin Cancer Res. 2010;29:32 pubmed publisher
    ..The metanalysis showed that exon-selectivity is an important signature of cancer type reflecting different contexts in which tumours arise. ..
  46. Maira S, Pecchi S, Huang A, Burger M, Knapp M, Sterker D, et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther. 2012;11:317-28 pubmed publisher
    Following the discovery of NVP-BEZ235, our first dual pan-PI3K/mTOR clinical compound, we sought to identify additional phosphoinositide 3-kinase (PI3K) inhibitors from different chemical classes with a different selectivity profile...
  47. Bader A, Kang S, Vogt P. Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc Natl Acad Sci U S A. 2006;103:1475-9 pubmed
    ..The in vivo oncogenicity of PIK3CA mutants in an avian species strongly suggests a critical role for these mutated proteins in human malignancies. ..
  48. Deregibus M, Cantaluppi V, Doublier S, Brizzi M, Deambrosis I, Albini A, et al. HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells. J Biol Chem. 2002;277:25195-202 pubmed
  49. Chugh P, Fan S, Planelles V, Maggirwar S, Dewhurst S, Kim B. Infection of human immunodeficiency virus and intracellular viral Tat protein exert a pro-survival effect in a human microglial cell line. J Mol Biol. 2007;366:67-81 pubmed
    ..showed that the pro-survival effects of intracellular Tat could be attributed to activation of the PI-3-kinase (PI3K)/Akt pathway in the microglial cell line...
  50. Huang C, Mandelker D, Schmidt Kittler O, Samuels Y, Velculescu V, Kinzler K, et al. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science. 2007;318:1744-8 pubmed
    ..In addition to providing new insights about the structure of PI3Kalpha, these results suggest specific mechanisms for the effect of oncogenic mutations in p110alpha and p85alpha. ..
  51. Lerma E, Catasus L, Gallardo A, Peiro G, Alonso C, Aranda I, et al. Exon 20 PIK3CA mutations decreases survival in aggressive (HER-2 positive) breast carcinomas. Virchows Arch. 2008;453:133-9 pubmed publisher
    ..Exon 20 PIK3CA mutations are relatively frequent in Her-2+ tumors and shorten survival, whereas neither exons 9 and 20 mutations seem related with "triple negative" breast carcinomas. ..
  52. Vasudevan K, Barbie D, Davies M, Rabinovsky R, McNear C, Kim J, et al. AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer. Cancer Cell. 2009;16:21-32 pubmed publisher
    Dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer...
  53. Platt F, Hurst C, Taylor C, Gregory W, Harnden P, Knowles M. Spectrum of phosphatidylinositol 3-kinase pathway gene alterations in bladder cancer. Clin Cancer Res. 2009;15:6008-17 pubmed publisher
    The phosphatidylinositol 3-kinase (PI3K) pathway can be activated by alterations affecting several pathway components...
  54. Fariña Sarasqueta A, Zeestraten E, van Wezel T, van Lijnschoten G, van Eijk R, Dekker J, et al. PIK3CA kinase domain mutation identifies a subgroup of stage III colon cancer patients with poor prognosis. Cell Oncol (Dordr). 2011;34:523-31 pubmed publisher
    ..In stage I and II this negative effect on outcome was not seen. PIK3CA mutation in exon 20 is a negative prognostic factor in stage III colon cancer patients. Moreover, this negative effect is not present in stage I and II patients. ..
  55. Meyer D, Brinkhaus H, Müller U, Muller M, Cardiff R, Bentires Alj M. Luminal expression of PIK3CA mutant H1047R in the mammary gland induces heterogeneous tumors. Cancer Res. 2011;71:4344-51 pubmed publisher
    The phosphoinositide 3-kinase (PI3K) signaling cascade, a key mediator of cellular survival, growth, and metabolism, is frequently altered in human cancer...
  56. Whitehall V, Rickman C, Bond C, Ramsnes I, Greco S, Umapathy A, et al. Oncogenic PIK3CA mutations in colorectal cancers and polyps. Int J Cancer. 2012;131:813-20 pubmed publisher
    ..2%) and 1/4 (25.0%) tubulovillous adenomas with a focus of cancer. These data provide insight into the molecular events driving traditional versus serrated pathway tumorigenesis. ..
  57. Muller C, Miller C, Hofmann W, Gross M, Walsh C, Kawamata N, et al. Rare mutations of the PIK3CA gene in malignancies of the hematopoietic system as well as endometrium, ovary, prostate and osteosarcomas, and discovery of a PIK3CA pseudogene. Leuk Res. 2007;31:27-32 pubmed
    ..Additionally, a previously unidentified PIK3CA pseudogene spanning exons 9-13 on chromosome 22 was discovered. ..
  58. Pang H, Flinn R, Patsialou A, Wyckoff J, Roussos E, Wu H, et al. Differential enhancement of breast cancer cell motility and metastasis by helical and kinase domain mutations of class IA phosphoinositide 3-kinase. Cancer Res. 2009;69:8868-76 pubmed publisher
    Class IA (p85/p110) phosphoinositide 3-kinases play a major role in regulating cell growth, survival, and motility...
  59. Hao Y, Wang C, Cao B, Hirsch B, Song J, Markowitz S, et al. Gain of interaction with IRS1 by p110?-helical domain mutants is crucial for their oncogenic functions. Cancer Cell. 2013;23:583-93 pubmed publisher
    PIK3CA, which encodes the p110? catalytic subunit of phosphatidylinositol 3-kinase ?, is frequently mutated in human cancers...
  60. Abubaker J, Bavi P, Al Harbi S, Ibrahim M, Siraj A, Al Sanea N, et al. Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population. Oncogene. 2008;27:3539-45 pubmed publisher
    Activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway results in an increase in cell proliferation and survival...
  61. Ehrenschwender M, Siegmund D, Wicovsky A, Kracht M, Dittrich Breiholz O, Spindler V, et al. Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation. Cell Death Differ. 2010;17:1435-47 pubmed publisher
    Constitutively active PI3K catalytic subunit alpha (PIK3CA) interfered with apoptosis induction downstream of death receptor-signaling complex formation allowing robust caspase-8 activation without triggering the execution steps of ..
  62. Campbell I, Russell S, Choong D, Montgomery K, Ciavarella M, Hooi C, et al. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res. 2004;64:7678-81 pubmed
    ..5% of all ovarian cancers and 45% of the endometrioid and clear cell subtypes. Our study is the first direct evidence that PIK3CA is an oncogene in ovarian cancer and greatly extends recent findings in breast cancer. ..
  63. Tian S, Simon I, Moreno V, Roepman P, Tabernero J, Snel M, et al. A combined oncogenic pathway signature of BRAF, KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction. Gut. 2013;62:540-9 pubmed publisher
    ..51, p<0.0009). A combined oncogenic pathway signature allows the identification of patients with an active EGFR-signalling pathway that could benefit from downstream pathway inhibition. ..
  64. Liao X, Morikawa T, Lochhead P, Imamura Y, Kuchiba A, Yamauchi M, et al. Prognostic role of PIK3CA mutation in colorectal cancer: cohort study and literature review. Clin Cancer Res. 2012;18:2257-68 pubmed publisher
    Mutations in PIK3CA [the gene encoding the p110? catalytic subunit of phosphatidylinositide-3-kinase (PI3K)] play an important role in colorectal carcinogenesis...
  65. Nosho K, Kawasaki T, Ohnishi M, Suemoto Y, Kirkner G, Zepf D, et al. PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations. Neoplasia. 2008;10:534-41 pubmed
    ..In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level. ..
  66. Maruyama N, Miyoshi Y, Taguchi T, Tamaki Y, Monden M, Noguchi S. Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women. Clin Cancer Res. 2007;13:408-14 pubmed
    ..PIK3CA mutations seem to have a potential to be used as an indicator of favorable prognosis. ..
  67. Berg M, Danielsen S, Ahlquist T, Merok M, Agesen T, Vatn M, et al. DNA sequence profiles of the colorectal cancer critical gene set KRAS-BRAF-PIK3CA-PTEN-TP53 related to age at disease onset. PLoS ONE. 2010;5:e13978 pubmed publisher
  68. Garcia Dios D, Lambrechts D, Coenegrachts L, Vandenput I, Capoen A, Webb P, et al. High-throughput interrogation of PIK3CA, PTEN, KRAS, FBXW7 and TP53 mutations in primary endometrial carcinoma. Gynecol Oncol. 2013;128:327-34 pubmed publisher
  69. Mitra A, Raychaudhuri S, Raychaudhuri S. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade. Cytokine. 2012;60:38-42 pubmed publisher
    ..b>PI3K/Akt/mTOR signaling cascade plays crucial role in cell growth and survival...
  70. Carpenter C, Duckworth B, Auger K, Cohen B, Schaffhausen B, Cantley L. Purification and characterization of phosphoinositide 3-kinase from rat liver. J Biol Chem. 1990;265:19704-11 pubmed
    ..Substitution of Mn2+ for Mg2+ results in only approximately 10% of the Mg2(+)-dependent activity. Physiological calcium concentrations have no effect on the enzyme activity. Phosphoinositide 3-kinase has a broad pH optimum around 7. ..
  71. Edgar K, Wallin J, Berry M, Lee L, Prior W, Sampath D, et al. Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors. Cancer Res. 2010;70:1164-72 pubmed publisher
    Therapeutic inhibitors are being developed against the phosphoinositide 3-kinase (PI3K) pathway, the deregulation of which drives tumor growth and survival in many cancers. There are eight PI3Ks in mammals divided into three classes...
  72. Sun M, Hart J, Hillmann P, Gymnopoulos M, Vogt P. Addition of N-terminal peptide sequences activates the oncogenic and signaling potentials of the catalytic subunit p110? of phosphoinositide-3-kinase. Cell Cycle. 2011;10:3731-9 pubmed publisher
    Addition of short (6 to 16 amino acids) peptide sequences to the N-terminus of p110? induces a gain of function. Such sequences include the common Flag, His, and VSV tags as well as random sequences...
  73. Ellis M, Lin L, Crowder R, Tao Y, Hoog J, Snider J, et al. Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer. Breast Cancer Res Treat. 2010;119:379-90 pubmed publisher
    ..Nonetheless, as with other recent studies, a favorable interaction between PIK3CA KD mutation and prognosis was detected. The mechanism for the favorable prognostic impact of PIK3CA mutation status therefore remains unexplained. ..
  74. Chaft J, Arcila M, Paik P, Lau C, Riely G, Pietanza M, et al. Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling. Mol Cancer Ther. 2012;11:485-91 pubmed publisher
    ..alpha polypeptide (PIK3CA) encodes the p110? subunit of the mitogenic signaling protein phosphoinositide 3-kinase (PI3K)...
  75. Herreros Villanueva M, Gomez Manero N, Muñiz P, Garcia Giron C, Coma Del Corral M. PIK3CA mutations in KRAS and BRAF wild type colorectal cancer patients. A study of Spanish population. Mol Biol Rep. 2011;38:1347-51 pubmed publisher
    ..PIK3CA mutation may be considered as it could be a hypothetic reason to be not responder to anti-EGFR antibodies. ..
  76. Perrone F, Lampis A, Orsenigo M, Di Bartolomeo M, Gevorgyan A, Losa M, et al. PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol. 2009;20:84-90 pubmed publisher
    ..in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear...
  77. Ikenoue T, Kanai F, Hikiba Y, Obata T, Tanaka Y, Imamura J, et al. Functional analysis of PIK3CA gene mutations in human colorectal cancer. Cancer Res. 2005;65:4562-7 pubmed
    Mutations in the PIK3CA gene, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been reported in human cancers, including colorectal cancer...
  78. Sun M, Hillmann P, Hofmann B, Hart J, Vogt P. Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha. Proc Natl Acad Sci U S A. 2010;107:15547-52 pubmed publisher
    ..Studies with isoform-specific inhibitors of p110 suggest that expression of p85 mutants in fibroblasts leads exclusively to an activation of p110alpha, and ..
  79. Cizkova M, Cizeron Clairac G, Vacher S, Susini A, Andrieu C, Lidereau R, et al. Gene expression profiling reveals new aspects of PIK3CA mutation in ERalpha-positive breast cancer: major implication of the Wnt signaling pathway. PLoS ONE. 2010;5:e15647 pubmed publisher
    The PI3K/AKT pathway plays a pivotal role in breast cancer development and maintenance...
  80. Jackson S, Schoenwaelder S, Goncalves I, Nesbitt W, Yap C, Wright C, et al. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med. 2005;11:507-14 pubmed
    ..In this study we have defined a key role for the Type Ia phosphoinositide 3-kinase (PI3K) p110beta isoform in regulating the formation and stability of integrin alpha(IIb)beta(3) adhesion bonds, necessary ..
  81. Abubaker J, Bavi P, Al Haqawi W, Jehan Z, Munkarah A, Uddin S, et al. PIK3CA alterations in Middle Eastern ovarian cancers. Mol Cancer. 2009;8:51 pubmed publisher
    ..Expression of PIK3CA protein expression (p110 alpha), PTEN, p-AKT and Ki-67 was analyzed by immunohistochemistry. PIK3CA amplification was seen in 54 of 152 (35...
  82. Samuels Y, Velculescu V. Oncogenic mutations of PIK3CA in human cancers. Cell Cycle. 2004;3:1221-4 pubmed
    ..To determine whether PI3Ks are genetically altered in human cancers, we recently analyzed the sequences of the PI3K gene family and discovered that one member, the PIK3CA gene encoding the p110alpha catalytic subunit, was ..
  83. Dong Y, Yang X, Wong O, Zhang X, Liang Y, Zhang Y, et al. PIK3CA mutations in endometrial carcinomas in Chinese women: phosphatidylinositol 3'-kinase pathway alterations might be associated with favorable prognosis. Hum Pathol. 2012;43:1197-205 pubmed publisher
    ..Furthermore, the function of the phosphatidylinositol 3'-kinase pathway might be affected by estrogen receptor status. ..
  84. Kang S, Seo S, Chang H, Yoo C, Park S, Dong S. Mutual exclusiveness between PIK3CA and KRAS mutations in endometrial carcinoma. Int J Gynecol Cancer. 2008;18:1339-43 pubmed publisher
    ..PIK3CA was frequently mutated in endometrial cancers. KRAS and PIK3CA mutations are inversely correlated, suggesting that genetic alterations of KRAS and PIK3CA may play equivalent roles in endometrial carcinogenesis. ..
  85. Mori R, Ishiguro H, Kimura M, Mitsui A, Sasaki H, Tomoda K, et al. PIK3CA mutation status in Japanese esophageal squamous cell carcinoma. J Surg Res. 2008;145:320-6 pubmed publisher
    ..We performed a cell proliferation assay to determine the effects of a PI3K inhibitor LY294002. In exon 9, a somatic mutation was found in two patients (2.2%) and in two cell lines...
  86. Janku F, Wheler J, Westin S, Moulder S, Naing A, Tsimberidou A, et al. PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. J Clin Oncol. 2012;30:777-82 pubmed publisher
    Mutations of the PIK3CA gene may predict response to phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) inhibitors...
  87. Qiu W, Tong G, Manolidis S, Close L, Assaad A, Su G. Novel mutant-enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer. Int J Cancer. 2008;122:1189-94 pubmed
    ..g., breast cancer, colorectal cancer), the abilities to detect PIK3CA mutations with enhanced sensitivities have great potential impacts on target therapies for many cancer types. ..
  88. Jia S, Roberts T, Zhao J. Should individual PI3 kinase isoforms be targeted in cancer?. Curr Opin Cell Biol. 2009;21:199-208 pubmed publisher
    Activation of the phosphoinositide-3-kinase (PI3K) signaling pathway is frequently found in common human cancers, brought about by oncogenic receptor tyrosine kinases (RTKs) acting upstream, PTEN loss, or activating mutations of PI3K ..
  89. Dupont Jensen J, Laenkholm A, Knoop A, Ewertz M, Bandaru R, Liu W, et al. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer. Clin Cancer Res. 2011;17:667-77 pubmed publisher
    PIK3CA mutations are frequent in breast cancer and activate the PI3K/Akt pathway. Unexpectedly, PIK3CA mutation appears in general to be associated with better outcome...
  90. Janku F, Lee J, Tsimberidou A, Hong D, Naing A, Falchook G, et al. PIK3CA mutations frequently coexist with RAS and BRAF mutations in patients with advanced cancers. PLoS ONE. 2011;6:e22769 pubmed publisher
    ..mutations of PIK3CA, RAS (KRAS, NRAS), and BRAF have been identified in various malignancies, and activate the PI3K/AKT/mTOR and RAS/RAF/MEK pathways, respectively. Both pathways are critical drivers of tumorigenesis...
  91. Janku F, Wheler J, Naing A, Falchook G, Hong D, Stepanek V, et al. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res. 2013;73:276-84 pubmed publisher
    PIK3CA mutations may predict response to PI3K/AKT/mTOR inhibitors in patients with advanced cancers, but the relevance of mutation subtype has not been investigated...
  92. Velho S, Oliveira C, Ferreira A, Ferreira A, Suriano G, Schwartz S, et al. The prevalence of PIK3CA mutations in gastric and colon cancer. Eur J Cancer. 2005;41:1649-54 pubmed
    A wide variety of tumours show PIK3CA mutations leading to increased phosphatidylinositol-3 kinase (PI3K) activity...