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

Massachusetts General Hospital

Novartis Institutes for BioMedical Research

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

Massachusetts General Hospital

Brigham and Women's Hospital

Jiang Chen

Massachusetts General Hospital

Christopher R. Chin

Massachusetts Institute of Technology (MIT)

Zohreh Amoozgar

Massachusetts General Hospital

Raphael Ferreira

Massachusetts Institute of Technology (MIT)

Chalmers, Biologi och bioteknik, Systembiologi

Ivy X. Chen

Massachusetts General Hospital

Kamila Naxerova

Massachusetts General Hospital

Harvard Medical School

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

Harvard Medical School

University of Michigan

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

Hackensack Meridian Health

Rutgers University

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. 2 414-428

Ämneskategorier

Farmaceutisk vetenskap

Farmakologi och toxikologi

Cancer och onkologi

DOI

10.1038/s43018-021-00183-y

Mer information

Senast uppdaterat

2021-04-27