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PHD3 Loss in Cancer Enables Metabolic Reliance on Fatty Acid Oxidation via Deactivation of ACC2.
German, Natalie J; Yoon, Haejin; Yusuf, Rushdia Z; Murphy, J Patrick; Finley, Lydia W S; Laurent, Gaëlle; Haas, Wilhelm; Satterstrom, F Kyle; Guarnerio, Jlenia; Zaganjor, Elma; Santos, Daniel; Pandolfi, Pier Paolo; Beck, Andrew H; Gygi, Steven P; Scadden, David T; Kaelin, William G; Haigis, Marcia C.
Afiliación
  • German NJ; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Yoon H; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Yusuf RZ; Stem Cell and Regenerative Biology Department, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Murphy JP; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Finley LW; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Laurent G; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Haas W; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Satterstrom FK; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Guarnerio J; Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
  • Zaganjor E; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Santos D; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Pandolfi PP; Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
  • Beck AH; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
  • Gygi SP; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
  • Scadden DT; Stem Cell and Regenerative Biology Department, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Kaelin WG; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Haigis MC; Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA. Electronic address: marcia_haigis@hms.harvard.edu.
Mol Cell ; 63(6): 1006-20, 2016 09 15.
Article en En | MEDLINE | ID: mdl-27635760
While much research has examined the use of glucose and glutamine by tumor cells, many cancers instead prefer to metabolize fats. Despite the pervasiveness of this phenotype, knowledge of pathways that drive fatty acid oxidation (FAO) in cancer is limited. Prolyl hydroxylase domain proteins hydroxylate substrate proline residues and have been linked to fuel switching. Here, we reveal that PHD3 rapidly triggers repression of FAO in response to nutrient abundance via hydroxylation of acetyl-coA carboxylase 2 (ACC2). We find that PHD3 expression is strongly decreased in subsets of cancer including acute myeloid leukemia (AML) and is linked to a reliance on fat catabolism regardless of external nutrient cues. Overexpressing PHD3 limits FAO via regulation of ACC2 and consequently impedes leukemia cell proliferation. Thus, loss of PHD3 enables greater utilization of fatty acids but may also serve as a metabolic and therapeutic liability by indicating cancer cell susceptibility to FAO inhibition.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetil-CoA Carboxilasa / Prolina / Leucemia Mieloide Aguda / Regulación Neoplásica de la Expresión Génica / Ácidos Grasos / Prolina Dioxigenasas del Factor Inducible por Hipoxia Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetil-CoA Carboxilasa / Prolina / Leucemia Mieloide Aguda / Regulación Neoplásica de la Expresión Génica / Ácidos Grasos / Prolina Dioxigenasas del Factor Inducible por Hipoxia Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos