Department of Cancer Biology, Prostate Cancer Discovery and Development Program, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cancer Cell. 2010 Jan 19;17(1):53-64. doi: 10.1016/j.ccr.2009.11.021.
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.
凋亡抑制蛋白（IAP）在肿瘤进展中起作用，但该途径的要求尚不清楚。在这里，我们表明 XIAP 和 survivin 之间的分子间合作刺激肿瘤细胞侵袭并促进转移。该途径不依赖于 IAP 抑制细胞死亡。相反，survivin-XIAP 复合物激活 NF-κB，进而导致纤维连接蛋白基因表达增加，β1 整合素信号传导以及细胞运动激酶 FAK 和 Src 的激活。因此，IAPs 是直接的转移基因，其拮抗剂可能为癌症患者提供抗转移治疗。
