Regulation and function of pyruvate kinase M2 in cancer

•PKM2 functions as a protein kinase to regulate gene expression.•PKM2 but not PKM1 translocates into the nucleus upon growth factor stimulation.•Nuclear PKM2 promotes growth factor-induced Warburg effect.

Altered metabolism is fundamental to the growth and survival of cancer cells. Pyruvate kinase M2 (PKM2), a key enzyme in cancer metabolism, has been demonstrated to play a central role not only in metabolic reprogramming but also in direct regulation of gene expression and subsequent cell cycle progression. This review outlines the current understanding of PKM2 protein kinase activity and regulatory mechanisms underlying PKM2 expression, enzymatic activity, and nuclear localization, thus highlighting PKM2 as a potential therapeutic target.