The SWI/SNF complex in tumor metabolism: Mechanisms and therapeutic implications

Cancer metabolic reprogramming is a driver of tumorigenesis and progression. While extensive research has highlighted the roles of metabolic enzymes and signaling pathways in this process, the mechanisms by which chromatin regulation coordinates the metabolic network at the transcriptional level remain unclear. The SWI/SNF chromatin remodeling complex, a key epigenetic regulator, has recently been shown to modulate multiple tumor metabolic pathways. Metabolic reprogramming induced by mutations in its subunits has garnered increasing attention, but comprehensive reviews on how SWI/SNF-mediated chromatin remodeling governs this process are limited. This paper examines how the SWI/SNF complex regulates metabolic gene transcription by positioning promoters and enhancer regions, guided by transcription factors, and remodeling nucleosome structures. It further discusses its role in regulating glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, lipid metabolism, and the coupling of carbon-nitrogen metabolism between amino acids and glucose-lipid metabolism. Focusing on subunit mutations such as ARID1A, SMARCA4, and PBRM1, this paper explores their impact on metabolic adaptation, offering insights for identifying therapeutic targets. Based on these findings, a combination intervention strategy targeting the protein levels of glutaminase 1, oxidative phosphorylation (complex I), glutamine transport, and glycolysis is proposed. By integrating SWI/SNF complex status and metabolic phenotypes, a therapeutic framework is developed that balances metabolic compensation blockade and enhanced cell death sensitivity, providing a more precise treatment strategy for metabolism-dependent tumors.