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Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer.
Maguire, Olivia A; Ackerman, Sarah E; Szwed, Sarah K; Maganti, Aarthi V; Marchildon, François; Huang, Xiaojing; Kramer, Daniel J; Rosas-Villegas, Adriana; Gelfer, Rebecca G; Turner, Lauren E; Ceballos, Victor; Hejazi, Asal; Samborska, Bozena; Rahbani, Janane F; Dykstra, Christien B; Annis, Matthew G; Luo, Ji-Dung; Carroll, Thomas S; Jiang, Caroline S; Dannenberg, Andrew J; Siegel, Peter M; Tersey, Sarah A; Mirmira, Raghavendra G; Kazak, Lawrence; Cohen, Paul.
Afiliação
  • Maguire OA; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-institutional MD-PhD Program, New York, NY 10065, USA.
  • Ackerman SE; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA; AAAS Science and Technology Policy Fellow in the Office of Global Health, Health Workforce Branch, U.S. Agency for International Development, Washington, D.C. 20547, USA.
  • Szwed SK; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-institutional MD-PhD Program, New York, NY 10065, USA.
  • Maganti AV; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA.
  • Marchildon F; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA.
  • Huang X; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Kramer DJ; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA; Weill Cornell/Rockefeller/Sloan Kettering Tri-institutional MD-PhD Program, New York, NY 10065, USA.
  • Rosas-Villegas A; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA.
  • Gelfer RG; Weill Cornell/Rockefeller/Sloan Kettering Tri-institutional MD-PhD Program, New York, NY 10065, USA.
  • Turner LE; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA.
  • Ceballos V; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA.
  • Hejazi A; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA.
  • Samborska B; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada.
  • Rahbani JF; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada.
  • Dykstra CB; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada.
  • Annis MG; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
  • Luo JD; Bioinformatics Resource Center, The Rockefeller University, New York, NY 10065, USA.
  • Carroll TS; Bioinformatics Resource Center, The Rockefeller University, New York, NY 10065, USA.
  • Jiang CS; Rockefeller University Hospital, The Rockefeller University, New York, NY 10065, USA.
  • Dannenberg AJ; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
  • Siegel PM; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada.
  • Tersey SA; Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
  • Mirmira RG; Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
  • Kazak L; Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3G1Y6, Canada.
  • Cohen P; Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY 10065, USA. Electronic address: pcohen@rockefeller.edu.
Cell Metab ; 33(3): 499-512.e6, 2021 03 02.
Article em En | MEDLINE | ID: mdl-33596409
Obesity is a major risk factor for adverse outcomes in breast cancer; however, the underlying molecular mechanisms have not been elucidated. To investigate the role of crosstalk between mammary adipocytes and neoplastic cells in the tumor microenvironment (TME), we performed transcriptomic analysis of cancer cells and adjacent adipose tissue in a murine model of obesity-accelerated breast cancer and identified glycine amidinotransferase (Gatm) in adipocytes and Acsbg1 in cancer cells as required for obesity-driven tumor progression. Gatm is the rate-limiting enzyme in creatine biosynthesis, and deletion in adipocytes attenuated obesity-driven tumor growth. Similarly, genetic inhibition of creatine import into cancer cells reduced tumor growth in obesity. In parallel, breast cancer cells in obese animals upregulated the fatty acyl-CoA synthetase Acsbg1 to promote creatine-dependent tumor progression. These findings reveal key nodes in the crosstalk between adipocytes and cancer cells in the TME necessary for obesity-driven breast cancer progression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Comunicação Celular / Creatina / Obesidade Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans Idioma: En Revista: Cell Metab Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Comunicação Celular / Creatina / Obesidade Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans Idioma: En Revista: Cell Metab Ano de publicação: 2021 Tipo de documento: Article