IAP regulation of metastasis.
Inhibitor-of-Apoptosis (IAP) proteins contribute to tumor progression, but the requirements of this pathway are not understood. Here, we show that intermolecular cooperation between XIAP and survivin stimulates tumor cell invasion and promotes metastasis. This pathway is independent of IAP inhibition of cell death. Instead, a survivin-XIAP complex activates NF-kappaB, which in turn leads to increased fibronectin gene expression, signaling by beta1 integrins, and activation of cell motility kinases FAK and Src. Therefore, IAPs are direct metastasis genes, and their antagonists could provide antimetastatic therapies in patients with cancer.
Department of Cancer Biology, Prostate Cancer Discovery and Development Program, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Swarna
S
Mehrotra
Lucia R
LR
Languino
Christopher M
CM
Raskett
Arthur M
AM
Mercurio
Takehiko
T
Dohi
Dario C
DC
Altieri
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000502:physiology*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D000077022:Survivin