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Rock2 promotes the invasion and metastasis of hepatocellular carcinoma by modifying MMP2 ubiquitination and degradation
Authors:Da Huang  Xiaohong Du  Rongfa Yuan  Leifeng Chen  Tiande Liu  Chongyu Wen  Mingwen Huang  Ming Li  Liang Hao  Jianghua Shao
Affiliation:1. Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China;2. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China;3. Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, Nanchang, China;4. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China
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.
Keywords:Hepatocellular carcinoma   Invasion   Metastasis   Rock2   MMP2   Ubiquitination
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