Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others. Plays a role in the positive regulation of phagocytosis and pinocytosis.

1. We identified a total of five distinct mutations in PIK3CA (NM_006218.2), including one hotspot mutation (c.1624G>A;p.Glu542Lys); two recurrent, strong (gain of function) mutations (c.3140A>T;p.His1047Leu, c.1258T>C;p.Cys420Arg); one previously described mutation in patients with macrodactyly (c.344G>C;p.Arg115Pro); and one novel somatic PIK3CA mutation (c.248T>C; p.Phe83Ser) not previously described PMID: 29446767
2. PIK3CA mutation in gastric cancer is a rare finding. It is strongly associated with the microsatellite instability (MSI) molecular subgroup, presenting a worse outcome than other MSI patients. A completely different outcome is associated with the mutation in exon 9 compared to the mutation in exon 20, with the latter being more favorable. PMID: 29905413
3. In early breast cancer, PIK3CA mutations seem to identify HER2+ patients who are less likely to reach pCR. The clinical implications of PIK3CA mutations tend to vary between exon 9 and exon 20. This mechanism should be explored in further studies. PMID: 29575819
4. miR152 may have an important role in pancreatic beta cell function, and established an association between miR152 and the PI3Kalpha axis. PMID: 30106118
5. The majority of PIK3CA H1047R mutations in the breast cancer cohort precede genome doubling. PMID: 29170395
6. in Stage I colorectal cancer presence of KRAS mutations, that of simultaneous mutations in PIK3CA gene, or that of multiple KRAS mutations was significantly associated with shorter cancer specific survival; PIK3CA or multiple KRAS mutations were associated with nodal micrometastases and poorly differentiated clusters G3 as well PMID: 30018674
7. CTNNB1 mutations were found in 60% of Basal cell adenoma but not in basal cell adenocarcinoma. None of the tested cases had PIK3CA mutations. CTNNB1 mutation trended to be more common in those cases having a predominant tubular or tubulotrabecular patterns. PMID: 29224720
8. The crucial role of p110beta and the more subtle role of p110alpha in the production of PIP3 molecular species following platelet stimulation has been demonstrated. PMID: 29902570
9. High PI3K expression is associated with metastasis in ovarian cancer. PMID: 29739299
10. phenotypic changes in metabolism following a single copy knock-in of mutant PIK3CA (H1047R) in the MCF10A cell line, an important cell model for studying oncogenic transformation in breast tissues, were examined. PMID: 28393905
11. The PIK3CA and PIK3R1 impactful mutations exhibit a mutually exclusive pattern, leading to oncogenesis and hyperactivity of PI3K pathway in breast cancer. PMID: 29636477
12. PIK3CA mutation is associated with decreased risk of peritoneal metastases in chemo-resistant metastatic colorectal cancer. PMID: 29380640
13. High PIK3CA expression is associated with metastasis via epithelialmesenchymal transition carcinoma in colorectal cancer. PMID: 30066935
14. High expression of PI3KCA is associated with drug resistance and proliferation of breast cancer. PMID: 28165066
15. High PI3K expression is associated with periodontitis. PMID: 30218719
16. We validated the presence of IDH2 R172 hotspot mutations and PIK3CA hotspot mutations in 100% and 67% of solid papillary breast carcinoma with reverse polarity tested, respectively PMID: 29603332
17. High PIK3CA expression is associated with metastasis in colon cancer. PMID: 29305742
18. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data PMID: 30227836
19. Our results indicate that low-grade adenosquamous carcinoma of the breast of the breast is a low-grade triple-negative breast cancer that harbours a basal-like phenotype with no androgen receptor expression, and shows a high rate of PIK3CA mutations PMID: 29537649
20. Multivariate analyses revealed that the PIK3CA mutation and clinical T stage were independent favorable prognostic factors (hazard ratio 0.34, 95% confidence interval: 0.12-0.96, p = 0.042). PIK3CA mutations were significantly associated with APC alterations (p = 0.0007) and BRAF mutations (p = 0.0090). PMID: 30115035
21. higher frequency of ESR1 and PIK3CA mutations in the plasma than in the serum in 33 MBC patients; therefore, serum samples should not be considered the preferred source of cfDNA. PMID: 29689710
22. When considered together (43 cases), 1/25 cases (4%) with a PIK3CA mutation and/or low PTEN expression levels had a pathologic complete response (pCR)compared to 7/18 cases (39%) with wild-type PI3KCA and high PTEN expression levels (p = 0.006). PMID: 29110152
23. PI3K is a signal linker between L-selectin and PSGL-1 in IL-18 transcriptional activation at the promoter level. PMID: 29218606
24. The role of PI3K in cancer has been well established, and mutations of PIK3CA, the gene coding for catalytic subunit p110alpha of PI3K, are found in approximately 30% human cancers. we review the structures and activation modes of PI3Ks and its implications in angiogenesis, extracellular matrix remodeling and tumor immunity. PMID: 29219001
25. Double mutation of PIK3CA and TP53 is an independent predictive factor for overall survival in stage II/III colorectal cancer patients receiving 5-FU-based chemotherapy. PMID: 29434452
26. High PI3K expression is associated with cervical cancer. PMID: 29328485
27. High PIK3CA expression is associated with head and neck carcinoma. PMID: 29506489
28. pK15-dependent signaling may occur from intracellular vesicles and rely on the endocytotic machinery. Specifically, a class II PI3K, PI3K-C2alpha, is recruited by pK15 and involved in pK15-dependent intracellular signaling and viral reactivation from latency. PMID: 29950425
29. The data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in colorectal cancer and suggest that targeting glutamine metabolism may be an effective approach to treat patients harboring PIK3CA mutations. PMID: 27321283
30. High Resolution Melting Analysis can be used as a rapid and sensitive method for mutation screening. Dysregulation of PIK3CA gene in bladder cancer reveals its potentials as a mechanistic link for cancer development, which in turn suggests its special use in interventional studies for targeted therapy PMID: 29353467
31. In patients without PIK3CA alteration, TP53 nonfunctional mutations are associated with poor prognosis. PMID: 29714670
32. Knowing the mutation status of KRAS, BRAF or PIK3CA in stage II colorectal cancer can significantly improve the accuracy of prognoses. PMID: 28685592
33. Survival analyses revealed that PIK3CA mutation was a significant prognostic factor for poor overall survival [multivariate adjusted hazard ratio (HR), 3.9; 95% confidence interval (95% CI), 1.3-11.8; P = .017] and cancer-specific survival (multivariate adjusted HR, 3.6; 95% CI, 1.2-11.0; P = .024) in stage IIB to IVA cervical cancers treated by concurrent chemoradiotherapy with weekly cisplatin. PMID: 30075505
34. Oncogenic PIK3CA alters methionine and cysteine utilization, partly by inhibiting xCT to contribute to the methionine dependency phenotype in human breast cancer cells. PMID: 29259101
35. The bladder cancer cell line TCCSUP, which harbors a PIK3CA E545K mutation, was sensitive to pictilisib compared to cell lines with wild-type PIK3CA Pictilisib exhibited stronger antitumor activity in bladder cancer patient-derived xenografts models with PI3KCA H1047R mutation or amplification than the control patient-derived xenografts model PMID: 28808038
36. By monitoring single-cell dynamics in each of these contexts, the authors identified PI3K/Akt regulation of glycolysis as a multifaceted modulator of single-cell metabolic dynamics that is required to maintain metabolic stability in proliferating cells. PMID: 29239720
37. results suggest that c-Jun, p38 MAPK, PIK3CA/Akt, and GSK3 signaling involved in the effect of miR-203 on the proliferation of hepatocellular carcinoma cells. PMID: 28887744
38. these results suggest that aspirin inhibited human uterine leiomyoma cell growth by regulating KRasp110alpha interaction. Aspirin which targeting on interaction between K-Ras and p110alpha may serve as a new therapeutic drug for uterine leiomyoma treatment. PMID: 28849118
39. PIK3CA mutation is a distinctive genetic feature of NSCLC with COPD, regardless of age, smoking dose, pathological stage, and histology. PMID: 29191607
40. In this study of 71 patients with advanced solid tumors who had received prior treatments (86% of whom were PIK3CA mutated), 3 different dose schedules of TAK-117 were evaluated. The MTD of TAK-117 was established as 150 mg once daily and 900 mg for both intermittent (MWF/MTuW) schedules. PMID: 28490463
41. Results show that head and neck squamous cell carcinoma tumors with low P120CTN and PI3K pathway mutations have higher levels of MMP1 compared to tumors with high P120CTN and no PI3K pathway mutations demonstrating that P120CTN downregulation and PIK3CA mutations promote MMP1-driven invasion. PMID: 28637905
42. Case Reports: PIK3CA mutations are present in multiple tissues of facial infiltrating lipomatosis. PMID: 28665924
43. p85alpha plays a tumor-suppressive role in transformation; p110alpha-selective therapeutics may be effective in the treatment of breast cancer patients with PIK3R1 loss PMID: 28630349
44. High Expressions of PI3K is associated with metastasis of esophageal squamous cell carcinoma. PMID: 28418888
45. E545K missense mutation of PIK3CA is associated with loss of protein stability and development of breast cancer. PMID: 27581627
46. while telomere length did not correlate with the presence of a mutation in BRAF (V-raf murine sarcoma viral oncogene homolog B), PIK3CA (phosphatidylinositol 3-kinase catalytic subunit), or MSI status, it was significantly associated with the occurrence of a mutation in KRAS PMID: 28850092
47. The combination of SAR256212 and SAR245408 resulted in stable disease as the best response. Side effects seen in combination were similar to the profiles of each individual drug. Patient outcome was the same regardless of tumor PI3KCA mutation status PMID: 28031425
48. High expression of PI3K is associated with nasopharyngeal carcinoma. PMID: 28586035
49. Study showed for the first time that co-occuring oncogenic HER2 and mutant PIK3CA could induce replication stress in mammary epithelial cells and drives breast cancer progression. PMID: 28902361
50. Mosaic gain of function mutation in PIK3CA gene leads to abnormal AKT-mTOR pathway activation and is responsible of the clinical manifestations. PMID: 28577738

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PI3/PI4-kinase family

HGNC: 8975

OMIM: 114480

KEGG: hsa:5290

STRING: 9606.ENSP00000263967

UniGene: Hs.553498