Branched-Chain Amino Acid Metabolism in Cancer Biology

Branched‐chain amino acids (BCAAs)—leucine, isoleucine and valine—serve not only as fundamental substrates for protein synthesis but also as versatile regulators of cellular metabolism and signalling. Cancer cells frequently upregulate BCAA transporters, such as SLC7A5, to satisfy elevated anabolic and bioenergetic demands. Once internalised, BCAAs are transaminated by cytosolic (BCAT1) or mitochondrial (BCAT2) aminotransferases to generate corresponding branched‐chain α‐keto acids, which may enter the tricarboxylic acid cycle or fuel lipid and nucleotide synthesis. The branched‐chain α‐keto acid dehydrogenase complex further commits these intermediates to oxidative catabolism. Through modulation of nutrient‐sensing pathways—most notably the mechanistic target of rapamycin complex 1 (mTORC1)—and provision of acetyl‐CoA or other anabolic precursors, BCAA metabolism interfaces directly with oncogenic signalling, cell growth, survival and metastasis. Dysregulation of enzyme expression, post‐translational modifications and organ-specific metabolic wiring underpins tumour heterogeneity, influences therapeutic resistance and offers avenues for biomarker development and targeted intervention.

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Branched-Chain Amino Acid Metabolism in Cancer Biology publication trend

The graph below shows the total number of articles in branched-chain amino acid metabolism in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Branched‐chain amino acids (BCAAs): Essential amino acids (leucine, isoleucine, valine) involved in protein synthesis and metabolic signalling.

BCAT1/BCAT2: Branched‐chain aminotransferases that catalyse the reversible transamination of BCAAs to branched‐chain α‐keto acids in the cytosol (BCAT1) or mitochondria (BCAT2).

Branched‐chain α‐keto acid dehydrogenase (BCKDH): A mitochondrial multienzyme complex that irreversibly decarboxylates branched‐chain α‐keto acids, committing them to oxidation.

mTORC1: Mechanistic target of rapamycin complex 1, a central nutrient‐sensing kinase complex that integrates amino acid availability with cell growth and anabolic metabolism.

Epithelial–mesenchymal transition (EMT): A phenotypic shift enabling epithelial cells to acquire mesenchymal traits, facilitating invasion and metastasis.

References

1. Branched-chain amino acid metabolism in cancer. Current Opinion in Clinical Nutrition & Metabolic Care (2017).
2. Branched-chain amino acids sustain pancreatic cancer growth by regulating lipid metabolism. Experimental & Molecular Medicine (2019).
3. Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth. Signal Transduction and Targeted Therapy (2020).
4. BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism. Cell Death & Disease (2021).