ROCK2 promotes HCC proliferation by CEBPD inhibition through phospho-GSK3β/β-catenin signaling

FEBS Lett. 2015 Apr 13;589(9):1018-25. doi: 10.1016/j.febslet.2015.03.004. Epub 2015 Mar 12.

Abstract

Rho-associated kinase 2 (Rock2) is known to promote tumorigenesis in hepatocellular carcinoma (HCC). CCAAT/enhancer-binding protein delta (CEBPD) functions as a tumor suppressor. In this study, we found that the expression of Rock2 and CEBPD are inversely correlated. Knockdown of Rock2 increased CEBPD expression and inhibited the proliferation of HCC cells in vitro and in vivo. Mechanistically, we found that Rock2 regulates CEBPD expression through the p-GSK3β/β-catenin pathway. Taken together, we identified a novel Rock2-p-GSK3β/β-catenin-CEBPD regulatory circuitry, the dysfunction of which may contribute to the tumorigenic characteristic of HCC.

Keywords: CCAAT/enhancer-binding protein delta; Hepatocellular carcinoma; Proliferation; Rho-associated kinase 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CCAAT-Enhancer-Binding Protein-delta / genetics
  • CCAAT-Enhancer-Binding Protein-delta / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Hep G2 Cells
  • Humans
  • Mice, Nude
  • Phosphorylation
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Xenograft Model Antitumor Assays / methods
  • beta Catenin / metabolism*
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • CEBPD protein, human
  • CTNNB1 protein, human
  • beta Catenin
  • CCAAT-Enhancer-Binding Protein-delta
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • ROCK2 protein, human
  • rho-Associated Kinases
  • Glycogen Synthase Kinase 3