PIK3CA
phosphoinositide-3-kinase, catalytic, alpha polypeptide
catalytic subunit of a kinase which phosphorylates phosphatidylinositol and its phosphorylated derivatives at the 3' position of the inositol ring, generating secondary messengers that control cellular activities and properties including proliferation, survival, motility and morphology [Pubmed]; effector of ras [Pubmed]
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role in cancer | oncogene |
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differentiation and development | crucial for the differentiation of the nascent vascular plexus into arteries and veins [Pubmed]; oncogenic Pik3ca(H1047R) activates a multipotent genetic program in normally lineage-restricted populations at the early stage of tumour initiation in breast cancer [Pubmed] |
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types of alteration in cancer | frequently amplified in lung cancer [Pubmed]; recurrent missense somatic mutations: H1047R, H1047L, E545K, E545A, E542K, Q546K, R88Q [Pubmed] |
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impact of mutation on function | E542K, E545K, and H1047R mutations induce an oncogenic transformation with high efficiency; transforming ability is correlated with elevated catalytic activity in in vitro kinase assays [Pubmed]; E545K helical domain mutant proteins gain new interaction with IRS1, which stabilises PIK3CA independently of its canonical partner - p85, and lacks the p85's ability to inhibit the lipid kinase activity of PIK3CA [Pubmed] |
angiogenesis
activated by VEFR, required for vessel development and remodelling [Pubmed]
escaping programmed cell death
cells harbouring PIK3CA GOF mutations display resistance to growth factor deprivation induced apoptosis in colon carcinoma [Pubmed]; KD suppresses cell viability and induces apoptosis in glioblastoma T98G cell line [Pubmed]
proliferative signalling
physiological levels of Pik3ca H1047R GOF mutant results in ductal hyperplasia and formation of ER alpha-positive tumours in mouse mammary gland [Pubmed]; PIK3CA downregulation by miR-1 mimics led to a significant reduction of cell proliferation in NSCLC A549 cell line [Pubmed]; inhibition of PIK3CA activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumour regression in vivo in glioblastoma [Pubmed]; overexpression of miR-375, targeting PIK3CA, markedly suppressed cell proliferation in osteosarcoma [Pubmed]