AKT1
v-akt murine thymoma viral oncogene homolog 1
fibroblasts lacking Akt1 are resistant to transformation by mutant K-ras and stimulation by epidermal growth factor in lung cancer [Pubmed]; serine/threonine kinase, a component of PI3K/Akt pathway, activated by phosphatidylinositol 3,4,5-trisphosphate (PIP3), translocates to the cell membrane, where it's activated via phosphorylation [Pubmed]
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role in cancer | oncogene |
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types of alteration in cancer | amplified in gastric adenocarcinoma [Pubmed]; E17K was the only known driver alteration found in a subset of samples in breast cancer [Pubmed]; recurrent missense E17K [Pubmed] |
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impact of mutation on function | Lys 17 alters the electrostatic interactions of the lipid-binding pocket and forms new hydrogen bonds with a phosphoinositide ligand, resulting in hyperactivation of AKT1 by means of pathological localization to the plasma membrane and stimulation of downstream signalling [Pubmed] |
genome instability and mutations
E17K GOF mutant accelerates DSB repair and improves survival of irradiated cells in murine prostate cancer Tramp-C1 cell line [Pubmed]
angiogenesis
vital for the maintenance of vascular integrity, regulates the proliferation-apoptosis signalling during vascular remodelling, regulates various signalling pathways to affect the balance of pro- and anti-angiogenic factors [Pubmed]; promotes angiogenesis largely due to phosphorylation and regulation of important downstream effectors that promote aspects of angiogenic signalling [Pubmed]
escaping programmed cell death
KD inhibits anchorage-independent cell growth and induces apoptosis in cancer MiaPaCa-2, H460, HCT-15, and HT1080 cell line [Pubmed]; KD results in increased tumour cell apoptosis in response to serum starvation in haemangioma [Pubmed]; promotes growth factor independent survival in a kinase-independent way in melanocytes [Pubmed]; KD results in impaired cell survival in bladder carcinoma T24 cell line [Pubmed]; suppresses the cell apoptosis induced by DNA damage in colorectal cancer HCT116 and HT29 cell line [Pubmed]
proliferative signalling
PCAF-mediated Akt1 acetylation enhances Akt1 phosphorylation at both sites of Thr(308) and Ser(473) and promotes cell proliferation in glioblastoma [Pubmed]; KD results in impaired cell proliferation and colony formation in bladder carcinoma T24 cell line [Pubmed]; induces mammary hyperplasia in breast cancer [Pubmed]
invasion and metastasis
silencing of Akt1 increases the release of TGF-beta1, which induces a change of morphology, cancer cell dissociation, migration and eventually leads to EMT in lung cancer [Pubmed]; enforced expression of Akt1 induces cell migration and invasion in hepatocellular carcinoma HepG2 cell line [Pubmed]; enforced expression of Akt1 suppresses cell migration and invasion in colorectal cancer HCT116 cell line [Pubmed]; KD decreases basal and VEGF-stimulated cell migration in haemangioma [Pubmed]; KD results in impaired cell migration and microinvasion in bladder carcinoma T24 cell line [Pubmed]; inhibition of AKT1 signalling promotes invasion and metastasis of cancer cells with K-RAS or EGFR mutations in NSCLC [Pubmed]
change of cellular energetics
activation of ATK1 mimics insulin-induced glucose transport and protein synthesis in adipocytes and L6 myotubes [Pubmed]; AKT1 activation is associated with accumulation of aerobic glycolysis metabolites in prostate cancer [Pubmed]
suppression of growth
prevents HER2-driven tumorigenesis, in part through negative feedback inhibition of RTK signalling in breast cancer [Pubmed]