Cavin1 activates the Wnt/β-catenin pathway to influence the proliferation and migration of hepatocellular carcinoma

Ann Hepatol. 2024 Jan-Feb;29(1):101160. doi: 10.1016/j.aohep.2023.101160. Epub 2023 Sep 27.

Abstract

Introduction and objectives: Cavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression.

Materials and methods: Cavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis.

Results: Cavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished β-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression.

Conclusions: Cavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/β-catenin axis activation.

Keywords: Cancer progression; Epithelial-Mesenchymal Transition; Hepatomas; Tumor suppressor.

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / pathology
  • Wnt Signaling Pathway
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • CAVIN1 protein, human