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dc.contributor.authorBellovin, David I.
dc.contributor.authorSimpson, Kaylene J.
dc.contributor.authorDanilov, T.
dc.contributor.authorMaynard, Elizabeth
dc.contributor.authorRimm, David L.
dc.contributor.authorOettgen, Peter
dc.contributor.authorMercurio, Arthur M.
dc.date2022-08-11T08:08:02.000
dc.date.accessioned2022-08-23T15:39:52Z
dc.date.available2022-08-23T15:39:52Z
dc.date.issued2006-05-23
dc.date.submitted2010-11-07
dc.identifier.citationOncogene. 2006 Nov 2;25(52):6959-67. Epub 2006 May 22. <a href="http://dx.doi.org/10.1038/sj.onc.1209682">Link to article on publisher's site</a>
dc.identifier.issn0950-9232 (Linking)
dc.identifier.doi10.1038/sj.onc.1209682
dc.identifier.pmid16715134
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26273
dc.description.abstractUnderstanding how RhoC expression and activation are regulated is essential for deciphering its contribution to tumorigenesis. Here, we report that RhoC expression and activation are induced by the epithelial to mesenchymal transition (EMT) of colon carcinoma. Using LIM 1863 colon cancer cells, RhoC protein expression and subsequent activation were detected coincident with the loss of E-cadherin and acquisition of mesenchymal characteristics. Several Ets-1 binding sites were identified in the RhoC promoter, and evidence was obtained using chromatin immunoprecipitation that Ets-1 can regulate RhoC expression during the EMT. Interestingly, a marked decrease in RhoA activation associated with the EMT was observed that corresponds to the increase in RhoC expression. Use of shRNA established that RhoA inhibits and RhoC promotes post-EMT cell migration, demonstrating functional significance for their coordinate regulation. To assess the importance of RhoC expression in colon cancer, immunohistochemistry was performed on 566 colorectal tumors with known clinical outcome. The level of RhoC ranged from no expression to high expression, and statistical analysis revealed that elevated RhoC expression correlates with poor outcome as well as aberrant expression and localization of E-cadherin. These data provide one mechanism for how RhoC expression is regulated in colon carcinoma and substantiate its utility as a prognostic marker.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16715134&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1038/sj.onc.1209682
dc.subjectCadherins
dc.subjectCell Line, Tumor
dc.subjectColonic Neoplasms
dc.subjectEnzyme Activation
dc.subjectEpithelial Cells
dc.subjectHumans
dc.subjectImmunohistochemistry
dc.subjectImmunoprecipitation
dc.subjectNeoplasm Invasiveness
dc.subjectPrognosis
dc.subjectPromoter Regions, Genetic
dc.subjectProto-Oncogene Protein c-ets-1
dc.subjectRNA, Small Interfering
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectTranscription, Genetic
dc.subjectTumor Markers, Biological
dc.subjectrho GTP-Binding Proteins
dc.subjectrhoA GTP-Binding Protein
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleReciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma
dc.typeJournal Article
dc.source.journaltitleOncogene
dc.source.volume25
dc.source.issue52
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/187
dc.identifier.contextkey1633413
html.description.abstract<p>Understanding how RhoC expression and activation are regulated is essential for deciphering its contribution to tumorigenesis. Here, we report that RhoC expression and activation are induced by the epithelial to mesenchymal transition (EMT) of colon carcinoma. Using LIM 1863 colon cancer cells, RhoC protein expression and subsequent activation were detected coincident with the loss of E-cadherin and acquisition of mesenchymal characteristics. Several Ets-1 binding sites were identified in the RhoC promoter, and evidence was obtained using chromatin immunoprecipitation that Ets-1 can regulate RhoC expression during the EMT. Interestingly, a marked decrease in RhoA activation associated with the EMT was observed that corresponds to the increase in RhoC expression. Use of shRNA established that RhoA inhibits and RhoC promotes post-EMT cell migration, demonstrating functional significance for their coordinate regulation. To assess the importance of RhoC expression in colon cancer, immunohistochemistry was performed on 566 colorectal tumors with known clinical outcome. The level of RhoC ranged from no expression to high expression, and statistical analysis revealed that elevated RhoC expression correlates with poor outcome as well as aberrant expression and localization of E-cadherin. These data provide one mechanism for how RhoC expression is regulated in colon carcinoma and substantiate its utility as a prognostic marker.</p>
dc.identifier.submissionpathcancerbiology_pp/187
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages6959-67


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