title: Snail1 expression is required for sarcomagenesis.
abstract: Snail1 transcriptional repressor is a major inducer of epithelial-to mesenchymal transition but is very limitedly expressed in adult animals. We have previously demonstrated that Snail1 is required for the maintenance of mesenchymal stem cells (MSCs), preventing their premature differentiation. Now, we show that Snail1 controls the tumorigenic properties of mesenchymal cells. Increased Snail1 expression provides tumorigenic capabilities to fibroblastic cells; on the contrary, Snail1 depletion decreases tumor growth. Genetic depletion of Snail1 in MSCs that are deficient in p53 tumor suppressor downregulates MSC markers and prevents the capability of these cells to originate sarcomas in immunodeficient SCID mice. Notably, an analysis of human sarcomas shows that, contrarily to epithelial tumors, these neoplasms display high Snail1 expression. This is particularly clear for undifferentiated tumors, which are associated with poor outcome. Together, our results indicate a role for Snail1 in the generation of sarcomas.
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Alba-Castellón
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Batlle
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Francí
authors.affiliation: Servicio de Anatomía Patológica, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Fernández-Aceñero
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Rocco
authors.initials: R
authors.lastname: Mazzolini
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Peña
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: Jordina
authors.initials: J
authors.lastname: Loubat
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain; Servei d'Anatomia Patològica, Hospital del Mar, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Alameda
authors.affiliation: Departamento de Patología, Hospital Virgen de la Salud, Toledo, Spain.
authors.forename: Rufo
authors.initials: R
authors.lastname: Rodríguez
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Centre d'Estudis en Biofísica, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Josué
authors.initials: J
authors.lastname: Curto
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain; Servei d'Oncologia Mèdica, Hospital del Mar, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.affiliation: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Muñoz
authors.affiliation: Servicio de Oncología, Hospital Puerta de Hierro, Majadahonda, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ignacio Casal
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain; Servicio de Anatomía Patológica, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. Electronic address: agarcia@imim.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: García de Herreros
mesh_terms: D000818:Animals; D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors