PIK3CA

PIK3CA Background

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform is a protein in humans that is encoded by PIK3CA gene ^[1]. It is also called p110α due to its molecular weight. PIK3CA/p110α uses ATP to phosphorylate phosphatidylinositols (PtdIns), PtdIns4P, and PtdIns(4,5)P2 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. The involvement of p110α in human cancer has been hypothesized since 1995. Support for this hypothesis came from genetic and functional studies, including the discovery of common activating PIK3CA missense mutations in common human tumors ^[2]. It has been found to be oncogenic and is implicated in cervical cancers ^[3]. PIK3CA mutations are present in over one-third of breast cancers, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes (HER2 +).

[1] Hiles ID, Otsu M, et al. Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit [J]. Cell. 1992, 70 (3): 419–29.
[2] Samuels Y, Waldman T, et al. Oncogenic mutations of PIK3CA in human cancers [J]. Current Topics in Microbiology and Immunology. 2010, 347. Springer Berlin Heidelberg: 21–41.
[3] Ma YY, Wei SJ, et al. PIK3CA as an oncogene in cervical cancer [J]. Oncogene. 2000, 19 (23): 2739–44.