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The NAD+ Salvage Pathway Supports PHGDH-Driven Serine Biosynthesis.
Murphy, J Patrick; Giacomantonio, Michael A; Paulo, Joao A; Everley, Robert A; Kennedy, Barry E; Pathak, Gopal P; Clements, Derek R; Kim, Youra; Dai, Cathleen; Sharif, Tanveer; Gygi, Steven P; Gujar, Shashi.
Afiliación
  • Murphy JP; Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
  • Giacomantonio MA; Department of Pathology, Dalhousie University, Halifax, NS, Canada.
  • Paulo JA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  • Everley RA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  • Kennedy BE; Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
  • Pathak GP; Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
  • Clements DR; Department of Pathology, Dalhousie University, Halifax, NS, Canada.
  • Kim Y; Department of Pathology, Dalhousie University, Halifax, NS, Canada.
  • Dai C; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
  • Sharif T; Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
  • Gygi SP; Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Electronic address: steven_gygi@hms.harvard.edu.
  • Gujar S; Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada; Centre for Innovative and Collaborative Health Services Research, IWK Health Centre, Halifax, NS, Canada; Department of Biology, Dalhousie Univers
Cell Rep ; 24(9): 2381-2391.e5, 2018 08 28.
Article en En | MEDLINE | ID: mdl-30157431
ABSTRACT
NAD+ is a key metabolic redox cofactor that is regenerated from nicotinamide through the NAD+ salvage pathway. Here, we find that inhibiting the NAD+ salvage pathway depletes serine biosynthesis from glucose by impeding the NAD+-dependent protein, 3-phosphoglycerate dehydrogenase (PHGDH). Importantly, we find that PHGDHhigh breast cancer cell lines are exquisitely sensitive to inhibition of the NAD+ salvage pathway. Further, we find that PHGDH protein levels and those of the rate-limiting enzyme of NAD+ salvage, NAMPT, correlate in ER-negative, basal-like breast cancers. Although NAD+ salvage pathway inhibitors are actively being pursued in cancer treatment, their efficacy has been poor, and our findings suggest that they may be effective for PHGDH-dependent cancers.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Serina / Neoplasias de la Mama / Fosfoglicerato-Deshidrogenasa / NAD Límite: Female / Humans Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Serina / Neoplasias de la Mama / Fosfoglicerato-Deshidrogenasa / NAD Límite: Female / Humans Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Canadá