Department of Cell and Developmental Biology; Department of Pediatrics; Department of Biochemistry and Molecular Pharmacology; UMass Metabolic Network; Department of Radiology; Nickerson Lab; Imbalzano Lab
Biochemistry | Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Molecular Biology | Oncology
Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators. Reduction in lipid synthesis lowers proliferation rates, which can be restored by palmitate supplementation. This work has established BRG1 as an attractive target for breast cancer therapy. Unlike genetic alterations, epigenetic mechanisms are reversible, promising gentler therapies without permanent off-target effects at distant sites.
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Copyright: © 2017 Nickerson, Wu and Imbalzano. Citation: Front Oncol. 2017 Apr 4;7:49. doi: 10.3389/fonc.2017.00049. eCollection 2017. Link to article on publisher's site
SMARCA4, SWI/SNF, breast cancer, cancer metabolism, chromatin remodeling, epigenetic regulation, fatty acid synthesis pathway
Nickerson, Jeffrey A.; Wu, Qiong; and Imbalzano, Anthony N., "Mammalian SWI/SNF Enzymes and the Epigenetics of Tumor Cell Metabolic Reprogramming" (2017). UMass Metabolic Network Publications. 74.
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