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.
Ahn
Jee-Yin
JY
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
Hu
Yuanxin
Y
Kroll
Todd G
TG
Allard
Paulette
P
Ye
Keqiang
K
D017209:Apoptosis / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D020690:GTPase-Activating Proteins; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C485997:AGAP2 protein, human; D019204:GTP-Binding Proteins