Exploring the diverse role of pyruvate kinase M2 in cancer: Navigating beyond glycolysis and the Warburg effect

Pyruvate Kinase M2, a key enzyme in glycolysis, has garnered significant attention in cancer research due to its pivotal role in the metabolic reprogramming of cancer cells. Originally identified for its association with the Warburg effect, PKM2 has emerged as a multifaceted player in cancer biology. The functioning of PKM2 is intricately regulated at multiple levels, including controlling the gene expression via various transcription factors and non-coding RNAs, as well as adding post-translational modifications that confer distinct functions to the protein. Here, we explore the diverse functions of PKM2, encompassing newly emerging roles in non-glycolytic metabolic regulation, immunomodulation, inflammation, DNA repair and mRNA processing, beyond its canonical role in glycolysis. The ever-expanding list of its functions has recently grown to include roles in subcellular compartments such as the mitochondria and extracellular milieu as well, all of which make PKM2 an attractive drug target in the pursuit of therapeutics for cancer.