Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells

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• dc.contributor.author Celià-Terrassa, Tonica
• dc.contributor.author García de Herreros, Antonioca
• dc.contributor.author Thomson, Timothy M.ca
• dc.date.accessioned 2015-06-15T07:19:00Z
• dc.date.available 2015-06-15T07:19:00Z
• dc.date.issued 2012ca
• dc.description.abstract Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs.en
• dc.description.sponsorship Financial support was provided to T.M. Thomson by MICINN (SAF2008-04136-C02-01 and SAF2011-24686), the Agència de Gestió d’Ajuts Universitaris i de Recerca (2009SGR1482), the Agencia Española de Cooperación Internacional y Desarrollo (A/023859/09), and the Xarxa de Referencia en Biotecnologia; to P.L. Fernández by MICINN (FIS-PI080274), the Fondo de Investigaciones de la Seguridad Social (PI080274), the Spanish National Biobank Network, the Instituto de Salud Carlos III (ISCIII-RETIC RD06/0020), the Xarxa de Bancs de Tumours de Catalunya-Pla Director d’Oncologia, and the Fondo Europeo de Desarrollo Regional (FEDER) — Unión Europea “Una manera de hacer Europa”; and to R.R. Gomis by the BBVA Foundation and MICINN (SAF2007-62691)en
• dc.format.mimetype application/pdfca
• dc.identifier.citation Celia-Terrassa T, Meca-Cortes O, Mateo F, De Paz AM, Rubio N, Arnal-Estape A et al. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. Journal of Clinical Investigation. 2012;122(5):1849-68. DOI: 10.1172/JCI59218ca
• dc.identifier.doi http://dx.doi.org/10.1172/JCI59218
• dc.identifier.issn 0021-9738ca
• dc.identifier.uri http://hdl.handle.net/10230/23818
• dc.language.iso engca
• dc.publisher American Society for Clinical Investigationca
• dc.relation.ispartof Journal of Clinical Investigation. 2012;122(5):1849-68
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2008-04136
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-24686
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-62691
• dc.rights © American Society for Clinical Investigationca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Cèl·lules epitelialsca
• dc.subject.other Proteïnesca
• dc.subject.other Factors de transcripcióca
• dc.subject.other Antígensca
• dc.title Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cellsen
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca