title: Rock2 promotes the invasion and metastasis of hepatocellular carcinoma by modifying MMP2 ubiquitination and degradation.
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.
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China; Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
authors.forename: Da
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, Nanchang, China; Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China; Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
authors.forename: Rongfa
authors.initials: R
authors.lastname: Yuan
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China; Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
authors.forename: Leifeng
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China; Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
authors.forename: Tiande
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China; Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
authors.forename: Chongyu
authors.initials: C
authors.lastname: Wen
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China.
authors.forename: Mingwen
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China; Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China; Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, China; Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, China. Electronic address: shao5022@163.com.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Shao
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D059748:Proteolysis; D015398:Signal Transduction; D054875:Ubiquitination; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Hepatocellular carcinoma; Invasion; MMP2; Metastasis; Rock2; Ubiquitination