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dc.contributor.authorNiell, Núria
dc.contributor.authorLarriba, María Jesús
dc.contributor.authorFerrer-Mayorga, Gemma
dc.contributor.authorSánchez Pérez, María Isabel 
dc.contributor.authorCantero Cid, Ramón 
dc.contributor.authorReal, Francisco X.
dc.contributor.authordel Peso, Luis
dc.contributor.authorMuñoz, Alberto
dc.contributor.authorGonzález Sancho, José Manuel 
dc.contributor.otherUAM. Departamento de Bioquímicaes_ES
dc.contributor.otherInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)es_ES
dc.contributor.otherInstituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)es_ES
dc.date.accessioned2018-03-21T12:04:50Z
dc.date.available2018-03-21T12:04:50Z
dc.date.issued2018-02-15
dc.identifier.citationInternational Journal of Cancer 142.4 (2018): 792-804en_US
dc.identifier.issn0020-7136es_ES
dc.identifier.urihttp://hdl.handle.net/10486/681576
dc.description.abstractColorectal cancer results from the malignant transformation of colonic epithelial cells. Stromal fibroblasts are the main component of the tumour microenvironment, and play an important role in the progression of this and other neoplasias. Wnt/β-catenin signalling is essential for colon homeostasis, but aberrant, constitutive activation of this pathway is a hallmark of colorectal cancer. Here we present the first transcriptomic study on the effect of a Wnt factor on human colonic myofibroblasts. Wnt3A regulates the expression of 1,136 genes, of which 662 are upregulated and 474 are downregulated in CCD-18Co cells. A set of genes encoding inhibitors of the Wnt/β-catenin pathway stand out among those induced by Wnt3A, which suggests that there is a feedback inhibitory mechanism. We also show that the PKP2 gene encoding the desmosomal protein Plakophilin-2 is a novel direct transcriptional target of Wnt/β-catenin in normal and colon cancer-associated fibroblasts. PKP2 is induced by β-catenin/TCF through three binding sites in the gene promoter and one additional binding site located in an enhancer 20 kb upstream from the transcription start site. Moreover, Plakophilin-2 antagonizes Wnt/β-catenin transcriptional activity in HEK-293T cells, which suggests that it may act as an intracellular inhibitor of the Wnt/β-catenin pathway. Our results demonstrate that stromal fibroblasts respond to canonical Wnt signalling and that Plakophilin-2 plays a role in the feedback control of this effect suggesting that the response to Wnt factors in the stroma may modulate Wnt activity in the tumour cells.en_US
dc.description.sponsorshipGrant sponsor: Consejería de Educación, Juventud y Deporte, Comunidad de Madrid; Grant number: S2010/BMD-2344 Colomics2; Grant sponsor: Spanish Ministerio de Economía y Competitividad-Fondos FEDER; Grant numbers: Nurcamein SAF-2015-71878-REDT, SAF2013- 43468-R, SAF2014-53819-R; Grant sponsor: Instituto de la Salud Carlos III - Fondos FEDER; Grant number: CB16/12/00273 CIBERONC, RD12/0036/0021; Grant sponsor: Agencia Estatal de Investigación - Fondos FEDER; Grant number: SAF2016-76377-Ren_US
dc.format.extent13 pag.es_ES
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherJohn Wiley & Sons Ltd on behalf of UICCen_US
dc.relation.ispartofInternational Journal of Canceren_US
dc.rights© 2017 The Authorsen_US
dc.subject.otherColon canceren_US
dc.subject.otherGene regulationen_US
dc.subject.otherNormal and cancer-associated fibroblastsen_US
dc.subject.otherPKP2/Plakophilin-2en_US
dc.subject.otherWnt/β-catenin signallingen_US
dc.titleThe human PKP2/plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblastsen_US
dc.typearticleen
dc.subject.ecienciaMedicinaes_ES
dc.relation.publisherversionhttp://doi.org/10.1002/ijc.31104es_ES
dc.identifier.doi10.1002/ijc.31104es_ES
dc.identifier.publicationfirstpage792es_ES
dc.identifier.publicationissue4es_ES
dc.identifier.publicationlastpage804es_ES
dc.identifier.publicationvolume142es_ES
dc.relation.projectIDComunidad de Madrid. S2010/BMD-2344/Colomics 2es_ES
dc.relation.projectIDGobierno de España. SAF-2015-71878-REDTes_ES
dc.relation.projectIDGobierno de España. SAF2013- 43468-Res_ES
dc.relation.projectIDGobierno de España. SAF2014-53819-Res_ES
dc.relation.projectIDGobierno de España. CB16/12/00273 CIBERONCes_ES
dc.relation.projectIDGobierno de España. RD12/0036/0021es_ES
dc.relation.projectIDGobierno de España. SAF2016-76377-Res_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.rights.ccReconocimiento – NoComercial – SinObraDerivadaes_ES
dc.rights.accessRightsopenAccessen
dc.authorUAMNiell Garolera, Nuria (278877)
dc.authorUAMPeso Ovalle, Luis (260044)
dc.facultadUAMFacultad de Medicina
dc.institutoUAMInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
dc.institutoUAMInstituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)


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