Mammalian SWI/SNF Enzymes and the Epigenetics of Tumor Cell Metabolic Reprogramming.
paper
Cited
Public
- Authors
- Nickerson, Jeffrey A; Wu, Qiong; Imbalzano, Anthony N
- Year
- 2017
- Journal
- Frontiers in oncology
- PMID
- 28421159
- DOI
- 10.3389/fonc.2017.00049
- PMCID
- PMC5378717
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.
The chromatin remodeling enzyme Brahma-related gene 1 (BRG1) epigenetically regulates key enzymes in de novo fatty acid biosynthesis. The pathway for de novo fatty acid synthesis requires the enzymes ATP citrate lyase (ACLY), acetyl CoA carboxylase (ACC), and fatty acid synthase (FASN). ACLY is important for increasing cytoplasmic acetyl CoA to levels supportive of fatty acid synthesis. ACC is required for making malonyl CoA, which along with acetyl CoA is used by FASN to produce palmitate, a 16-carbon saturated fatty acid that can be extended and desaturated into the extended family of fatty acids which are used for fat storage and for the biosynthesis of membrane phospholipids. BRG1 is important for the transcription of ACLY, ACC, and FASN in breast cancer cells. Knockdown or inhibition of BRG1 decreases levels of all three enzymes with resulting decreases in lipid synthesis and decreases in breast tumor cell proliferation. Proliferation can be rescued with palmitate supplementation (28). Acetyl CoA is also the source of acetyl groups for histone acetylation which generally upregulates transcription and may cooperate with BRG1 in the regulation of gene expression.
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations. | 2017 | 28981154 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| NAA20-mediated ACF1 lactylation drives neuroblastoma progression through enhancing GCLM-dependent glutathione synthesis. | Han B et al. | — | 2026 | → |
| Chromatin and epigenetic regulation in malignant tumors: A comprehensive review. | Zhang X et al. | — | 2025 | → |
| Research progress of SWI/SNF complex in breast cancer. | Li K et al. | — | 2024 | → |
| The SWI/SNF chromatin remodeling complex: a critical regulator of metabolism. | Church MC et al. | — | 2024 | → |
| Tumor energy metabolism: implications for therapeutic targets. | Hu Y et al. | — | 2024 | → |
| Tumor suppressors RBL1 and PTEN are epigenetically silenced in IPF mesenchymal progenitor cells by a CD44/Brg1/PRMT5 regulatory complex. | Yang L et al. | — | 2024 | → |
| HMGB1 coordinates with Brahma-related gene 1 to promote epithelial-mesenchymal transition via the PI3K/Akt/mTOR pathway in BEAS-2B cells. | Deng X et al. | — | 2023 | → |
| INO80 function is required for mouse mammary gland development, but mutation alone may be insufficient for breast cancer. | Thang NX et al. | — | 2023 | → |
| PLK1 inhibition selectively induces apoptosis in ARID1A deficient cells through uncoupling of oxygen consumption from ATP production. | Srinivas US et al. | — | 2022 | → |
| The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo. | Smith JJ et al. | — | 2022 | → |
| A CD44/Brg1 nuclear complex confers mesenchymal progenitor cells with enhanced fibrogenicity in idiopathic pulmonary fibrosis. | Yang L et al. | — | 2021 | → |
| Human Placental Transcriptome Reveals Critical Alterations in Inflammation and Energy Metabolism with Fetal Sex Differences in Spontaneous Preterm Birth. | Lien YC et al. | — | 2021 | → |
| PLK1 inhibition selectively kills ARID1A deficient cells through uncoupling of oxygen consumption from ATP production | Srinivas US et al. | — | 2021 | — |
| The Chromatin Remodeling Protein BRG1 Regulates SREBP Maturation by Activating SCAP Transcription in Hepatocytes. | Kong M et al. | — | 2021 | → |
| Variation in SWI/SNF Chromatin Remodeling Complex Proteins is Associated with Alcohol Dependence and Antisocial Behavior in Human Populations. | Mathies LD et al. | — | 2017 | → |