Branched chain amino acid metabolism and cancer: the importance of keeping things in context

Elizabeth M. Selwan, Aimee L. Edinger


Because non-homeostatic proliferation increases anabolic demand, tumor cells reprogram metabolism in ways that support growth. Although tumor cells retain some metabolic flexibility, the constitutive activation of oncogenes and mutation or loss of tumor suppressors limits their metabolic choices and creates nutrient dependencies not present in their normal counterparts (1-8). Identifying and targeting these differences in metabolic wiring will likely be an effective means to limit tumor growth while sparing normal cells. Clearly, different oncogenic mutations activate distinct downstream gene expression programs that drive metabolic reprogramming in ways that favor certain biosynthetic routes. At the same time, oncogenic events occur in the divergent epigenetic landscapes associated with different tissues of origin. As normal lung and pancreatic cells from the same individual contain identical genomes yet exhibit markedly different gene expression patterns, it stands to reason that tumor cells with shared oncogenic drivers but different tissue origins would do the same.