PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt.
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Ahn JY, Hu Y, Kroll TG, Allard P, Ye K
PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt.
Proc Natl Acad Sci U S A. 2004 May 4;101(18):6993-8. Epub 2004 Apr 26.
- PubMed ID
- 15118108 [ View in PubMed]
- Abstract
PIKE-A (PIKE-activating Akt), an isoform of PIKE GTPase that enhances phosphatidylinositol 3-kinase (PI3-kinase) activity, specifically binds to active Akt but not PI3-kinase. PIKE-A stimulates Akt activity in a GTP-dependent manner and promotes invasiveness of cancer cell lines. Here, we show that PIKE-A is amplified in a variety of human cancers and that amplified PIKE-A directly stimulates Akt and inhibits apoptosis compared to cells with normal PIKE-A copy number. Overexpression of PIKE-A wild-type but not dominant-negative mutant stimulates Akt activity and prevents apoptosis. Moreover, knockdown of PIKE-A diminishes Akt activity and increases apoptosis. Our findings suggest that PIKE-A amplification contributes to cancer cell survival and progression by inhibiting apoptosis through up-regulating Akt.