Multifaceted role of branched-chain amino acid metabolism in cancer

Oncogene. 2020 Oct;39(44):6747-6756. doi: 10.1038/s41388-020-01480-z. Epub 2020 Sep 25.

Abstract

Metabolic reprogramming fulfils increased nutrient demands and regulates numerous oncogenic processes in tumors, leading to tumor malignancy. Branched-chain amino acids (BCAAs, i.e., valine, leucine, and isoleucine) function as nitrogen donors to generate macromolecules such as nucleotides and are indispensable for human cancer cell growth. The cell-autonomous and non-autonomous roles of altered BCAA metabolism have been implicated in cancer progression and the key proteins in the BCAA metabolic pathway serve as possible prognostic and diagnostic biomarkers in human cancers. Here we summarize how BCAA metabolic reprogramming is regulated in cancer cells and how it influences cancer progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acids, Branched-Chain / metabolism*
  • Animals
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Glutamic Acid / metabolism
  • Humans
  • Ketoglutaric Acids / metabolism
  • Metabolic Networks and Pathways / genetics
  • Metabolic Networks and Pathways / immunology
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Nitrogen / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Microenvironment*

Substances

  • Amino Acids, Branched-Chain
  • Ketoglutaric Acids
  • Reactive Oxygen Species
  • Glutamic Acid
  • Nitrogen