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FATTY ACID SYNTHESIS IS REQUIRED FOR BREAST CANCER BRAIN METASTASIS.
Ferraro, Gino B; Ali, Ahmed; Luengo, Alba; Kodack, David P; Deik, Amy; Abbott, Keene L; Bezwada, Divya; Blanc, Landry; Prideaux, Brendan; Jin, Xin; Posada, Jessica M; Chen, Jiang; Chin, Christopher R; Amoozgar, Zohreh; Ferreira, Raphael; Chen, Ivy X; Naxerova, Kamila; Ng, Christopher; Westermark, Anna M; Duquette, Mark; Roberge, Sylvie; Lindeman, Neal I; Lyssiotis, Costas A; Nielsen, Jens; Housman, David E; Duda, Dan G; Brachtel, Elena; Golub, Todd R; Cantley, Lewis C; Asara, John M; Davidson, Shawn M; Fukumura, Dai; Dartois, Véronique A; Clish, Clary B; Jain, Rakesh K; Vander Heiden, Matthew G.
Afiliação
  • Ferraro GB; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Ali A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Luengo A; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Kodack DP; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Deik A; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Abbott KL; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Bezwada D; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Blanc L; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Prideaux B; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Jin X; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Posada JM; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Chen J; The Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
  • Chin CR; Institut de Chimie & Biologie des Membranes & des Nano-objets, CNRS UMR 5248, Bordeaux, France.
  • Amoozgar Z; The Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
  • Ferreira R; Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston, TX, USA.
  • Chen IX; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
  • Naxerova K; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Ng C; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Westermark AM; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Duquette M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Roberge S; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Lindeman NI; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Lyssiotis CA; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
  • Nielsen J; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Housman DE; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Duda DG; Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Brachtel E; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Golub TR; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Cantley LC; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Asara JM; Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Davidson SM; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Fukumura D; Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Dartois VA; University of Michigan, Ann Arbor, MI, USA.
  • Clish CB; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
  • Jain RK; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Vander Heiden MG; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nat Cancer ; 2(4): 414-428, 2021 04.
Article em En | MEDLINE | ID: mdl-34179825
ABSTRACT
Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2 (HER2+) breast cancer, and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here, we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in brain. We determine that this phenotype is an adaptation to decreased lipid availability in brain relative to other tissues, resulting in a site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase (FASN) reduces HER2+ breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Neoplasias da Mama Limite: Female / Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Neoplasias da Mama Limite: Female / Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos