CAV1 promotes HCC cell progression and metastasis through Wnt/β-catenin pathway
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 an...
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Published in | PloS one Vol. 9; no. 9; p. e106451 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Conceived and designed the experiments: PYY LXQ YKL. Performed the experiments: HXY HLS. Analyzed the data: YZ FZ. Contributed reagents/materials/analysis tools: YKL. Wrote the paper: HXY. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0106451 |