PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt

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.