title: A novel FoxM1-caveolin signaling pathway promotes pancreatic cancer invasion and metastasis.
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.
authors.affiliation: Shanghai Key Laboratory of Pancreatic Diseases Research, Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Qiu
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Jia
authors.forename: Craig D
authors.initials: CD
authors.lastname: Logsdon
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Le
authors.forename: Daoyan
authors.initials: D
authors.lastname: Wei
authors.forename: Suyun
authors.initials: S
authors.lastname: Huang
authors.forename: Keping
authors.initials: K
authors.lastname: Xie
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D046888:Tissue Array Analysis; D014183:Transplantation, Heterologous
chemical_list: D051242:Caveolin 1; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors