TY - JOUR
T1 - IAP Regulation of Metastasis
AU - Mehrotra, Swarna
AU - Languino, Lucia R.
AU - Raskett, Christopher M.
AU - Mercurio, Arthur M.
AU - Dohi, Takehiko
AU - Altieri, Dario C.
N1 - Funding Information:
We thank Leslie Shaw for discussion, I.-S. Kim for a fibronectin promoter reporter construct, Michelle Kelliher for FSIPPW vector, Bert Vogelstein for HCT116 cells, Colin Duckett for XIAP −/− mouse embryonic fibroblasts and D148A/W310A XIAP cDNA, and Robert Sherwin for INS-1 cells. This work was supported by National Institutes of Health grants CA89720 (to L.R.L.); CA107548 (to A.M.M.); and CA78810, CA90917, CA118005, and HL54131 (to D.C.A.).
PY - 2010/1/19
Y1 - 2010/1/19
N2 - 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-κB, which in turn leads to increased fibronectin gene expression, signaling by β1 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.
AB - 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-κB, which in turn leads to increased fibronectin gene expression, signaling by β1 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.
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U2 - 10.1016/j.ccr.2009.11.021
DO - 10.1016/j.ccr.2009.11.021
M3 - Article
C2 - 20129247
AN - SCOPUS:73649095563
SN - 1535-6108
VL - 17
SP - 53
EP - 64
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -
