title: CAV1 promotes HCC cell progression and metastasis through Wnt/β-catenin pathway.
abstract: Caveolin-1 (CAV1) has significant roles in many primary tumors and metastasis, despite the fact that malignant cells from different cancer types have different profiles of CAV1 expression. There is little information concerning CAV1 expression and role in hepatocellular carcinoma (HCC) progresion and metastasis. The role of CAV1 in HCC progression was explored in this study. We reported that CAV1 was overexpressed in highly invasive HCC cell lines compared with poorly invasive ones. The immunohistochemical staining was obviously stronger in metastatic HCC samples than in the non-metastatic specimens via tissue microarrays. Furthermore, CAV1 overexpression enhanced HCC cell invasiveness in vitro, and promoted tumorigenicity and lung metastasis in vivo. By contrast, CAV1 stable knockdown markedly reduced these malignant behaviors. Importantly, we found that CAV1 could induce EMT process through Wnt/β-catenin pathway to promote HCC metastasis. We also identify MMP-7 as a novel downstream target of CAV1. We have determined that CAV1 acts as a mediator between hyperactive ERK1/2 signaling and regulation of MMP-7 transcription. Together, these studies mechanistically show a previously unrecognized interplay between CAV1, EMT, ERK1/2 and MMP-7 that is likely significant in the progression of HCC toward metastasis.
authors.affiliation: Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, P. R. China.
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, P. R. China.
authors.forename: Huali
authors.initials: H
authors.lastname: Shen
authors.affiliation: Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, P. R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, P. R. China; Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
authors.forename: Yinkun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, P. R. China; Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
authors.forename: Lunxiu
authors.initials: L
authors.lastname: Qin
authors.affiliation: Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, P. R. China; Department of Chemistry, Fudan University, Shanghai, P. R. China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
mesh_terms: D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D051242:Caveolin 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013347:Subcellular Fractions / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D051176:beta Catenin