UMMS Affiliation

Department of Cell and Developmental Biology; UMass Metabolic Network

Date

5-20-2016

Document Type

Article

Disciplines

Cancer Biology

Abstract

Cancer cells reprogram cellular metabolism to meet the demands of growth. Identification of the regulatory machinery that regulates cancer-specific metabolic changes may open new avenues for anti-cancer therapeutics. The epigenetic regulator BRG1 is a catalytic ATPase for some mammalian SWI/SNF chromatin remodeling enzymes. BRG1 is a well-characterized tumor suppressor in some human cancers, but is frequently overexpressed without mutation in other cancers, including breast cancer. Here we demonstrate that BRG1 upregulates de novo lipogenesis and that this is crucial for cancer cell proliferation. Knockdown of BRG1 attenuates lipid synthesis by impairing the transcription of enzymes catalyzing fatty acid and lipid synthesis. Remarkably, exogenous addition of palmitate, the key intermediate in fatty acid synthesis, rescued the cancer cell proliferation defect caused by BRG1 knockdown. Our work suggests that targeting BRG1 to reduce lipid metabolism and, thereby, to reduce proliferation, has promise for epigenetic therapy in triple negative breast cancer.

Rights and Permissions

Citation: Oncotarget. 2016 May 20. doi: 10.18632/oncotarget.9505. Link to article on publisher's site

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.

DOI of Published Version

10.18632/oncotarget.9505

Related Resources

Link to Article in PubMed

Keywords

BRG1, breast cancer, gene regulation, lipogenesis, metabolism

Journal Title

Oncotarget

PubMed ID

27223259

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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