Branched-chain amino acid metabolism in cancer.

Elitsa A Ananieva,Adam C Wilkinson

doi:10.1097/mco.0000000000000430

Abstract

Purpose of reviewThe current review aims to provide an update on the recent biomedical interest in oncogenic branched-chain amino acid (BCAA) metabolism, and discusses the advantages of using BCAAs and expression of BCAA-related enzymes in the treatment and diagnosis of cancers.Recent findingsAn accumulating body of evidence demonstrates that BCAAs are essential nutrients for cancer growth and are used by tumors in various biosynthetic pathways and as a source of energy. In addition, BCAA metabolic enzymes, such as the cytosolic branched-chain aminotransferase 1 (BCAT1) and mitochondrial branched-chain aminotransferase 2, have emerged as useful prognostic cancer markers. BCAT1 expression commonly correlates with more aggressive cancer growth and progression, and has attracted substantial scientific attention in the past few years. These studies have found the consequences of BCAT1 disruption to be heterogeneous; not all cancers share the same requirements for BCAA metabolites and the function of BCAT1 appears to vary between cancer types.SummaryBoth oncogenic mutations and cancer tissue-of-origin influence BCAA metabolism and expression of BCAA-associated metabolic enzymes. These new discoveries need to be taken into consideration during the development of new cancer therapies that target BCAA metabolism.

Highlights

Cancer cells have unlimited potential to divide and sustain growth
branched-chain amino acids (BCAAs) are essential for cancer growth and can act as mammalian target of rapamycin complex 1 agonists, building blocks for protein synthesis, and/or as sources of nitrogen and carbon
We summarize the latest discoveries on the utility of BCAT1 expression as a prognostic cancer cell marker and the recent mechanistic insights into how BCAT1 contributes to the metabolic reprograming of cancer cells

Summary

INTRODUCTION

Cancer cells have unlimited potential to divide and sustain growth This process is dependent on acquiring essential nutrients from the tumor microenvironment, which are used to maintain biomass and survival, even under conditions of poor nutrient and oxygen availability [1,2&,3]. Many cancer types overexpress enzymes that function to degrade amino acids, which provide cellular energy and metabolites for anabolic processes and serve as mechanisms of immune evasion by cancer cells [2&,5]. It has become evident that the enzymes catalyzing the first step in BCAA degradation are overexpressed in many cancers [10,11,12&] These are the cytosolic aDepartment of Biochemistry and Nutrition, Des Moines University, Des Moines, Iowa and bDepartment of Genetics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I.

KEY POINTS

CONCLUSION