Fatty acid synthesis is required for breast cancer brain metastasis
Name
nihms-1681647.pdf
Description
Accepted version
Size
5.92 MB
Format
Adobe PDF
Checksum (MD5)
cad830f1a8d102d2b2568225a9e6c519
Date Issued
April 1, 2021
Journal
Nature Cancer
Publisher
Springer Science and Business Media LLC
Citation
Ferraro, G.B., Ali, A., Luengo, A. et al. Fatty acid synthesis is required for breast cancer brain metastasis. Nat Cancer 2, 414–428 (2021)
Version
Author's final manuscript
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/S43018-021-00183-Y
