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

Area of Science:

• Epigenetics
• Cancer Biology
• Metabolic Pathways

Background:

• Cancer metabolic reprogramming drives tumorigenesis.
• SWI/SNF complex is a key epigenetic regulator modulating tumor metabolism.
• Mechanisms linking chromatin regulation to metabolic networks are unclear.

Purpose of the Study:

• To review how SWI/SNF chromatin remodeling governs cancer metabolic reprogramming.
• To explore the role of SWI/SNF in regulating key metabolic pathways.
• To identify therapeutic targets based on SWI/SNF mutations and metabolic phenotypes.

Main Methods:

• Examining SWI/SNF's regulation of metabolic gene transcription via chromatin remodeling.
• Analyzing SWI/SNF's role in glycolysis, TCA cycle, OXPHOS, and lipid metabolism.
• Investigating impacts of SWI/SNF subunit mutations (ARID1A, SMARCA4, PBRM1) on metabolic adaptation.

Main Results:

• SWI/SNF complex regulates metabolic gene transcription through promoter/enhancer positioning and nucleosome remodeling.
• SWI/SNF impacts glycolysis, TCA cycle, oxidative phosphorylation, lipid metabolism, and carbon-nitrogen metabolism.
• Mutations in SWI/SNF subunits like ARID1A, SMARCA4, and PBRM1 alter metabolic adaptation.

Conclusions:

• SWI/SNF chromatin remodeling is crucial for coordinating cancer cell metabolism.
• Targeting SWI/SNF-driven metabolic pathways offers therapeutic potential.
• A framework integrating SWI/SNF status and metabolic phenotypes enables precise treatment for metabolism-dependent cancers.