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

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.

• Authors: Ming Li, Wei Zhou, Rongfa Yuan, Leifeng Chen, Tiande Liu, Da Huang, Liang Hao, Yuancai Xie, Jianghua Shao
• Journal: FEBS letters (FEBS Lett) Vol. 589 Issue 9 Pg. 1018-25 (Apr 13 2015) ISSN: 1873-3468 [Electronic] England
• PMID: 25771860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• 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

Topics

• Animals
• Blotting, Western
• CCAAT-Enhancer-Binding Protein-delta (genetics, 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, metabolism)