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SIRT6 Suppresses Cancer Stem-like Capacity in Tumors with PI3K Activation Independently of Its Deacetylase Activity.
Ioris, Rafael M; Galié, Mirco; Ramadori, Giorgio; Anderson, Jason G; Charollais, Anne; Konstantinidou, Georgia; Brenachot, Xavier; Aras, Ebru; Goga, Algera; Ceglia, Nicholas; Sebastián, Carlos; Martinvalet, Denis; Mostoslavsky, Raul; Baldi, Pierre; Coppari, Roberto.
Afiliação
  • Ioris RM; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
  • Galié M; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Department of Neurosciences, Biomedicine and Movement, University of Verona, Verona 37134, Italy.
  • Ramadori G; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
  • Anderson JG; Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • Charollais A; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
  • Konstantinidou G; Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland.
  • Brenachot X; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
  • Aras E; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
  • Goga A; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
  • Ceglia N; Department of Computer Science University of California Irvine, Irvine, CA 92697, USA; Institute for Genomics and Bioinformatics, University of California Irvine, Irvine, CA 92697, USA.
  • Sebastián C; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA.
  • Martinvalet D; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
  • Mostoslavsky R; The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Baldi P; Department of Computer Science University of California Irvine, Irvine, CA 92697, USA; Institute for Genomics and Bioinformatics, University of California Irvine, Irvine, CA 92697, USA.
  • Coppari R; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland; Diabetes Center of the Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland. Electronic address: roberto.coppari@unige.ch.
Cell Rep ; 18(8): 1858-1868, 2017 02 21.
Article em En | MEDLINE | ID: mdl-28228253
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive cancer cells bear mutations that activate phosphatidylinositol-3-kinase (PI3K) signaling, and overexpression of SIRT6 reduces growth, progression, and grade of breast cancer in a mouse model with PI3K activation. Tumor metabolomic and transcriptomic analyses reveal that SIRT6 overexpression dampens PI3K signaling and stem-like characteristics and causes metabolic rearrangements in this cancer model. Ablation of a PI3K activating mutation in otherwise isogenic cancer cells is sufficient to convert SIRT6-sensitive into SIRT6-insensitive cells. SIRT6 overexpression suppresses PI3K signaling at the transcriptional level and antagonizes tumor sphere formation independent of its histone deacetylase activity. Our data identify SIRT6 as a putative molecular target that hinders stemness of tumors with PI3K activation.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Fosfatidilinositol 3-Quinases / Sirtuínas / Neoplasias Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Suíça
Texto completo
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Fosfatidilinositol 3-Quinases / Sirtuínas / Neoplasias Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Suíça