期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 18, 页码 6993-6998出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0400921101
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PIKE-A (PIKE-activating Akt), an isoform of PIKE GTPase that enhances phosphatidylinositol 3-kinase (P13-kinase) activity, specifically binds to active Akt but not P13-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.
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