File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: RhoE is frequently downregulated in HCC and suppresses HCC invasion through antagonizing the Rho/ROCK/MYPT pathway

TitleRhoE is frequently downregulated in HCC and suppresses HCC invasion through antagonizing the Rho/ROCK/MYPT pathway
Authors
Issue Date2012
Citation
Hepatology, 2012, v. 57 n. 1, p. 152-161 How to Cite?
AbstractDeregulation of Rho guanosine triphosphatase (GTPase) pathways plays an important role in tumorigenesis and metastasis of hepatocellular carcinoma (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 HCC. We examined the expression of RhoE in primary HCC samples from patients predominantly infected with the hepatitis B virus (HBV) and found that the RhoE messenger RNA (mRNA) level was frequently down-regulated (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 a lentiviral approach led to increased cell motility and invasiveness in SMMC7721 and BEL7402 HCC cells. Moreover, in vivo an 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/Rho-kinase (ROCK) pathway. CONCLUSION: RhoE was frequently down-regulated in predominantly HBV-associated HCCs and this down-regulation was associated with a more aggressive HCC phenotype. RhoE regulated the cytoskeleton remodeling and suppressed HCC motility and invasiveness by way of inhibiting the Rho/ROCK axis.
Persistent Identifierhttp://hdl.handle.net/10722/160058
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMa, Wen_US
dc.contributor.authorWong, CCLen_US
dc.contributor.authorTung, KKen_US
dc.contributor.authorWong, CMen_US
dc.contributor.authorNg, IOLen_US
dc.date.accessioned2012-08-16T06:02:09Z-
dc.date.available2012-08-16T06:02:09Z-
dc.date.issued2012en_US
dc.identifier.citationHepatology, 2012, v. 57 n. 1, p. 152-161en_US
dc.identifier.issn0270-9139en_US
dc.identifier.urihttp://hdl.handle.net/10722/160058-
dc.description.abstractDeregulation of Rho guanosine triphosphatase (GTPase) pathways plays an important role in tumorigenesis and metastasis of hepatocellular carcinoma (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 HCC. We examined the expression of RhoE in primary HCC samples from patients predominantly infected with the hepatitis B virus (HBV) and found that the RhoE messenger RNA (mRNA) level was frequently down-regulated (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 a lentiviral approach led to increased cell motility and invasiveness in SMMC7721 and BEL7402 HCC cells. Moreover, in vivo an 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/Rho-kinase (ROCK) pathway. CONCLUSION: RhoE was frequently down-regulated in predominantly HBV-associated HCCs and this down-regulation was associated with a more aggressive HCC phenotype. RhoE regulated the cytoskeleton remodeling and suppressed HCC motility and invasiveness by way of inhibiting the Rho/ROCK axis.-
dc.languageengen_US
dc.relation.ispartofHepatologyen_US
dc.titleRhoE is frequently downregulated in HCC and suppresses HCC invasion through antagonizing the Rho/ROCK/MYPT pathwayen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1527-3350 (Electronic) 0270-9139 (Linkin&volume=&spage=&epage=&date=2012&atitle=RhoE+is+frequently+downregulated+in+HCC+and+suppresses+HCC+invasion+through+antagonizing+the+Rho/ROCK/MYPT+pathwayen_US
dc.identifier.emailWong, CCL: carmencl@pathology.hku.hken_US
dc.identifier.emailTung, KK: edmund@pathology.hku.hken_US
dc.identifier.emailWong, CM: jackwong@pathology.hku.hken_US
dc.identifier.emailNg, IOL: iolng@hku.hken_US
dc.identifier.authorityWong, CCL=rp01602en_US
dc.identifier.authorityWong, CM=rp00231en_US
dc.identifier.doi10.1002/hep.25987-
dc.identifier.pmid22829315-
dc.identifier.scopuseid_2-s2.0-84872138430-
dc.identifier.hkuros204785en_US
dc.identifier.spage152-
dc.identifier.epage161-
dc.identifier.isiWOS:000313547700018-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats