| RhoE is frequently downregulated in HCC and suppresses HCC invasion through antagonizing the Rho/ROCK/MYPT pathway. | |
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MedLine Citation:
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PMID: 22829315 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Deregulation of Rho GTPase pathways plays an important role in tumorigenesis and metastasis of HCC. RhoE/Rnd3 belongs to an atypical subfamily of the RhoGTPase, the Rnd family, as it lacks the intrinsic GTPase activity and remains always in its active GTP-bound form. In this study, we investigated the role of RhoE in hepatocellular carcinoma (HCC). We examined the expression of RhoE in primary HCC samples from patients predominantly infected by hepatitis B virus and found that RhoE mRNA level was frequently downregulated (83.1%, 59/71) in HCCs. Low expression of RhoE in the tumors was significantly associated with shorter disease-free survival (P = 0.020) of the patients. Knockdown of RhoE by short-hairpin RNA using lentiviral approach led to increased cell motility and invasiveness in SMMC7721 and BEL7402 HCC cells. Moreover, in vivo orthotopic liver injection model in nude mice further demonstrated that knockdown of RhoE enhanced local invasion of HCC cells in the livers, with more invasive tumor front and increased incidence of venous invasion. Mechanistically, stable knockdown of RhoE in HCC cells significantly enhanced the phosphorylation of myosin phosphatase, promoted assembly of stress fibers, and increased the formation of plasma membrane blebbings, all these changes and activities being associated with activation of the Rho/ROCK pathway. Conclusion: RhoE was frequently downregulated in predominantly HBV-associated HCCs and this downregulation was associated with a more aggressive HCC phenotype. RhoE regulated the cytoskeleton remodeling and suppressed HCC motility and invasiveness via inhibiting the Rho/ROCK axis. (HEPATOLOGY 2012.). |
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Authors:
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Wei Ma; Carmen Chak-Lui Wong; Edmund Kwok-Kwan Tung; Chun Ming Wong; Irene Oi-Lin Ng |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-7-24 |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-7-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 American Association for the Study of Liver Diseases. |
Affiliation:
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State Key Laboratory for Liver Research, The University of Hong Kong; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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