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dc.contributor.authorHager, Martin H
dc.contributor.authorMorley, Samantha
dc.contributor.authorBielenberg, Diane R
dc.contributor.authorGao, Sizhen
dc.contributor.authorMorello, Matteo
dc.contributor.authorHolcomb, Ilona N
dc.contributor.authorLiu, Wennuan
dc.contributor.authorMouneimne, Ghassan
dc.contributor.authorDemichelis, Francesca
dc.contributor.authorKim, Jayoung
dc.contributor.authorSolomon, Keith R
dc.contributor.authorAdam, Rosalyn M
dc.contributor.authorIsaacs, William B
dc.contributor.authorHiggs, Henry N
dc.contributor.authorVessella, Robert L
dc.contributor.authorDi Vizio, Dolores
dc.contributor.authorFreeman, Michael R
dc.date.accessioned2013-04-26T18:57:34Z
dc.date.issued2012
dc.identifier.citationHager, Martin H., Samantha Morley, Diane R. Bielenberg, Sizhen Gao, Matteo Morello, Ilona N. Holcomb, Wennuan Liu, et al. 2012. Diaph3 governs the cellular transition to the amoeboid tumour phenotype. EMBO Molecular Medicine 4(8): 743-760.en_US
dc.identifier.issn1757-4676en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10589807
dc.description.abstractTherapies for most malignancies are generally ineffective once metastasis occurs. While tumour cells migrate through tissues using diverse strategies, the signalling networks controlling such behaviours in human tumours are poorly understood. Here we define a role for the Diaphanous-related formin-3 (DIAPH3) as a non-canonical regulator of metastasis that restrains conversion to amoeboid cell behaviour in multiple cancer types. The DIAPH3 locus is close to RB1, within a narrow consensus region of deletion on chromosome 13q in prostate, breast and hepatocellular carcinomas. DIAPH3 silencing in human carcinoma cells destabilized microtubules and induced defective endocytic trafficking, endosomal accumulation of EGFR, and hyperactivation of EGFR/MEK/ERK signalling. Silencing also evoked amoeboid properties, increased invasion and promoted metastasis in mice. In human tumours, DIAPH3 down-regulation was associated with aggressive or metastatic disease. DIAPH3-silenced cells were sensitive to MEK inhibition, but showed reduced sensitivity to EGFR inhibition. These findings have implications for understanding mechanisms of metastasis, and suggest that identifying patients with chromosomal deletions at DIAPH3 may have prognostic value.en_US
dc.language.isoen_USen_US
dc.publisherWILEY-VCH Verlagen_US
dc.relation.isversionofdoi:10.1002/emmm.201200242en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494074/pdf/en_US
dash.licenseLAA
dc.subjectcytoskeletonen_US
dc.subjectEGFRen_US
dc.subjectendocytosisen_US
dc.subjectmesenchymal-to-amoeboid transitionen_US
dc.subjectmetastasisen_US
dc.titleDIAPH3 Governs the Cellular Transition to the Amoeboid Tumour Phenotypeen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalEMBO Molecular Medicineen_US
dash.depositing.authorBielenberg, Diane R
dc.date.available2013-04-26T18:57:34Z
dc.identifier.doi10.1002/emmm.201200242*
dash.authorsorderedfalse
dash.contributor.affiliatedMouneimne, Ghassan
dash.contributor.affiliatedSolomon, Keith R.
dash.contributor.affiliatedFreeman, Michael R.
dash.contributor.affiliatedDi Vizio, Dolores
dash.contributor.affiliatedAdam, Rosalyn
dash.contributor.affiliatedGao, Sizhen
dash.contributor.affiliatedMorley, Samantha
dash.contributor.affiliatedKim, Jayoung
dash.contributor.affiliatedBielenberg, Diane


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