A recent review article published by Dr. Wen-Chun Hung, Deputy Director of National Institute of Cancer Research and his team in Molecular Cancer (2018 Feb 19;17(1):35), summarized current understanding of the role of pyruvate kinase M2-type (PKM2) in metabolic switch and gene regulation with emphasis on the recent progress of PKM2 in extracellular signaling and tumor microenvironment reprogramming. The review also discussed the discrepancy of some PKM2’s functions in vitro and in vivo, and the application of PKM2 in cancer detection and treatment.
PKM2, a metabolic enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway, has been shown to exhibit novel biological activities in the nucleus and outside the cells. Although cell-based studies reveal new non-canonical functions of PKM2 in gene transcription, epigenetic modulation and cell cycle progression, the importance of these non-canonical functions in PKM2-mediated tumorigenesis is still under debate because studies in genetically modified mice do not consistently echo the findings observed in cultured cancer cells. In addition to regulation of gene expression, the existence of PKM2 in exosomes opens a new venue to study the potential role of this glycolytic enzyme in cell-cell communication and extracellular signal initiation.
Hus MC; Hung WC. Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling. Molecular Cancer. 2018 Feb 19;17:Article number 35.