Fatty acid synthesis is required for breast cancer brain metastasis
Artikel i vetenskaplig tidskrift, 2021
Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2-positive 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 the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, resulting in site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase reduces human epidermal growth factor receptor 2-positive breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.
Författare
Gino B. Ferraro
Massachusetts General Hospital
Ahmed Ali
Massachusetts Institute of Technology (MIT)
Alba Luengo
Massachusetts Institute of Technology (MIT)
David P. Kodack
Novartis Institutes for BioMedical Research
Massachusetts General Hospital
Amy Deik
Massachusetts Institute of Technology (MIT)
Keene L. Abbott
Massachusetts Institute of Technology (MIT)
Divya Bezwada
Massachusetts General Hospital
Landry Blanc
Rutgers University
Institut de Chimie et de Biologie des Membranes et des Nano-Objets (CBMN)
Brendan Prideaux
The University of Texas at Austin
Rutgers University
Xin Jin
Massachusetts Institute of Technology (MIT)
Jessica M. Possada
Brigham and Women's Hospital
Massachusetts General Hospital
Jiang Chen
Massachusetts General Hospital
Christopher R. Chin
Massachusetts Institute of Technology (MIT)
Zohreh Amoozgar
Massachusetts General Hospital
Raphael Ferreira
Chalmers, Biologi och bioteknik, Systembiologi
Massachusetts Institute of Technology (MIT)
Ivy X. Chen
Massachusetts General Hospital
Kamila Naxerova
Harvard Medical School
Massachusetts General Hospital
Christopher Ng
Massachusetts Institute of Technology (MIT)
Anna M. Westermark
Massachusetts Institute of Technology (MIT)
Mark Duquette
Massachusetts General Hospital
Sylvie Roberge
Massachusetts General Hospital
Neal I. Lindeman
Brigham and Women's Hospital
Costas A. Lyssiotis
University of Michigan
Harvard Medical School
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
David E. Housman
Massachusetts Institute of Technology (MIT)
Dan G. Duda
Massachusetts General Hospital
Elena Brachtel
Harvard Medical School
Todd R. Golub
Massachusetts Institute of Technology (MIT)
Lewis C. Cantley
New York Presbyterian Hospital
Harvard Medical School
John M. Asara
Harvard Medical School
Shawn M. Davidson
Massachusetts Institute of Technology (MIT)
Princeton University
Dai Fukumura
Massachusetts General Hospital
Véronique A. Dartois
Rutgers University
Hackensack Meridian Health
Clary B. Clish
Massachusetts Institute of Technology (MIT)
Rakesh K. Jain
Massachusetts General Hospital
Matthew G. Vander Heiden
Massachusetts Institute of Technology (MIT)
Dana-Farber Cancer Institute
Nature Cancer
26621347 (eISSN)
Vol. 2 4 414-428Ämneskategorier
Farmaceutisk vetenskap
Farmakologi och toxikologi
Cancer och onkologi
DOI
10.1038/s43018-021-00183-y