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Cancer Res. 2012 Feb 1;72(3):655-65. doi: 10.1158/0008-5472.CAN-11-3102. Epub 2011 Dec 22.

A novel FoxM1-caveolin signaling pathway promotes pancreatic cancer invasion and metastasis.

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  • 1Shanghai Key Laboratory of Pancreatic Diseases Research, Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, PR China.

Abstract

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.

©2012 AACR.

PMID:
22194465
[PubMed - indexed for MEDLINE]
PMCID:
PMC3271134
Free PMC Article

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