A Novel FoxM1-Caveolin Signaling Pathway Promotes Pancreatic Cancer Invasion and Metastasis

作者：Huang, Chen; Qiu, Zhengjun; Wang, Liwei; Peng, Zhihai; Jia, Zhiliang; Logsdon, Craig D; Le, Xiangdong; Wei, Daoyan; Huang, Suyun; Xie, Keping^*

来源：Cancer Research, 2012, 72(3): 655-665.

DOI：10.1158/0008-5472.CAN-11-3102

Caveolin-1 (Cav-1), a principal structural component of caveolar membrane domains, contributes to cancer development but its precise functional roles and regulation remain unclear. In this study, we determined the oncogenic function of Cav-1 in preclinical models of pancreatic cancer and in human tissue specimens. Cav-1 expression levels correlated with metastatic potential and epithelial-mesenchymal transition (EMT) in both mouse and human pancreatic cancer cells. Elevated levels in cells promoted EMT, migration, invasion, and metastasis in animal models, whereas RNA interference (RNAi)-mediated knockdown inhibited these processes. We determined that levels of Cav-1 and the Forkhead transcription factor FoxM1 correlated directly in pancreatic cancer cells and tumor tissues. Enforced expression of FoxM1 increased Cav-1 levels, whereas RNAi-mediated knockdown of FoxM1 had the opposite effect. FoxM1 directly bound to the promoter region of Cav-1 gene and positively transactivated its activity. Collectively, our findings defined Cav-1 as an important downstream oncogenic target of FoxM1, suggesting that dysregulated signaling of this novel FoxM1-Cav-1 pathway promotes pancreatic cancer development and progression. Cancer Res; 72(3); 655-65.

• 出版日期2012-2-1
• 单位上海交通大学