Knockdown of CD44 inhibits proliferation, migration, and invasiveness in hepatocellular carcinoma cells by modulating CXCR4/Wnt/β-Catenin Axis

Acta Biochim Pol. 2023 Feb 3;70(1):117-122. doi: 10.18388/abp.2020_6319.

Abstract

Hepatocellular carcinoma (HCC) has high mortality and incidence worldwide. The molecular mechanism associated with HCC is largely unexplored.

Objective: To investigate the impact of CD44 knock-down on the proliferation, migration, and invasiveness in HCC cells.

Methods: Colony formation and MTT assay were used to observe cellular proliferation and viability. In addition, cellular invasion and migration were studied by Transwell and wound healing assays respectively. Finally, western blotting was utilized to check the protein expression levels.

Results: The cellular proliferation, invasion and metastasis in Huh7 cells were inhibited after the silencing of CD44. Furthermore, expression levels of MMP-2, MMP-9, CXCR4, GSK-3β and β-catenin was significantly decreased. However, opposite results were demonstrated when CD44 was overexpressed.

Conclusions: Interference with the expression of CD44 significantly inhibits the invasion and metastasis in the HCC cell line, Huh7. Furthermore, CD44 was found to regulate the expression of MMP-2, MMP-9, CXCL12, CXCR4 and Wnt/β-catenin signal pathway.

MeSH terms

  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Liver Neoplasms* / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness / genetics
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Glycogen Synthase Kinase 3 beta
  • CD44 protein, human
  • Hyaluronan Receptors
  • CXCR4 protein, human