1. Rock2 promotes the invasion and metastasis of hepatocellular carcinoma by modifying MMP2 ubiquitination and degradation
- Author
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Tiande Liu, Xiaohong Du, Jianghua Shao, Mingwen Huang, Chongyu Wen, Rongfa Yuan, Liang Hao, Leifeng Chen, Ming Li, and Da Huang
- Subjects
Carcinoma, Hepatocellular ,MMP2 ,Biophysics ,Mice, Nude ,Matrix metalloproteinase ,medicine.disease_cause ,Biochemistry ,Metastasis ,Mice ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,ROCK2 ,Molecular Biology ,rho-Associated Kinases ,Gene knockdown ,Chemistry ,Liver Neoplasms ,Ubiquitination ,Hep G2 Cells ,Cell Biology ,HCCS ,medicine.disease ,digestive system diseases ,Up-Regulation ,Gene Knockdown Techniques ,Proteolysis ,Cancer research ,Heterografts ,Matrix Metalloproteinase 2 ,Carcinogenesis ,Signal Transduction - Abstract
Rho-associated coiled-coil-containing protein kinase 2 (Rock2) is a downstream effector of Rho that plays an important role in the tumorigenesis and progression of hepatocellular carcinoma (HCC). Matrix metalloproteinase 2 (MMP2) is a master regulator of tumor metastasis. In this study, we investigated the collections of Rock2 and MMP2 in HCCs and determined the potential role and molecular mechanism of Rock2 in MMP2-mediated invasiveness and metastasis. We found that Rock2 and MMP2 were markedly overexpressed in HCCs compared with the corresponding adjacent tissues, where a positive correlation in their expression was found. The knockdown of Rock2 significantly decreased MMP2 expression and inhibited the invasion and metastasis of HCC in vitro and in vivo. Additionally, the upregulation of MMP2 rescued the decreased migration and invasion induced by the knockdown of Rock2, whereas the knockdown of MMP2 decreased Rock2-enhanced HCC migration and invasion. Mechanistically, Rock2 stabilized MMP2 by preventing its ubiquitination and degradation. Together, our results link two drivers of invasion and metastasis in HCC and identify a novel pathway for MMP2 control.
- Published
- 2014
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