title: Sox4 links tumor suppression to accelerated aging in mice by modulating stem cell activation.
abstract: Sox4 expression is restricted in mammals to embryonic structures and some adult tissues, such as lymphoid organs, pancreas, intestine, and skin. During embryogenesis, Sox4 regulates mesenchymal and neural progenitor survival, as well as lymphocyte and myeloid differentiation, and contributes to pancreas, bone, and heart development. Aberrant Sox4 expression is linked to malignant transformation and metastasis in several types of cancer. To understand the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display accelerated aging and reduced cancer incidence. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4(cKO)) in stratified epithelia. Sox4(cKO) mice show increased skin stem cell quiescence and resistance to chemical carcinogenesis concomitantly with downregulation of cell cycle, DNA repair, and activated hair follicle stem cell pathways. Altogether, these findings highlight the importance of Sox4 in regulating adult tissue homeostasis and cancer.
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Foronda
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Martínez
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schoeftner
authors.affiliation: Bioinformatics Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gómez-López
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: Ralph
authors.initials: R
authors.lastname: Schneider
authors.affiliation: Department of Animal Surgery and Pathology, Complutense University of Madrid, Madrid 28040, Spain.
authors.forename: Juana M
authors.initials: JM
authors.lastname: Flores
authors.affiliation: Bioinformatics Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain. Electronic address: mblasco@cnio.es.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000375:Aging / Q000235:genetics*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D004260:DNA Repair; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse