The BRG1 chromatin remodeling enzyme links cancer cell metabolism and proliferation

Qiong Wu, Pasil Madany, Jason R. Dobson, Jake M. Schnabl, Soni Sharma, Tara C. Smith, Andre J. van Wijnen, Janet L. Stein, Jane B. Lian, Gary S. Stein, Rohini Muthuswami, Anthony N. Imbalzano, Jeffrey A. Nickerson

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)38270-38281
Number of pages12
JournalOncotarget
Volume7
Issue number25
DOIs
StatePublished - 2016

Keywords

  • BRG1
  • Breast cancer
  • Gene regulation
  • Lipogenesis
  • Metabolism

ASJC Scopus subject areas

  • Oncology

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