The role of the M2 isoform of pyruvate kinase in cancer metabolism

Abstract

Several alterations in the functions of some regulatory proteins have been observed during cancer oncogenesis, as well as of proteins that are not usually involved in the control of cell cycle. Such is the case of isoform M2 of pyruvate kinase (PKM2), which is a key enzyme in the regulation of energetic metabolism in glycolytic pathway. PKM2 has been found to be involved mainly in tissues that carry out rapid cell division, mainly in neoplasms, during embryonic development and in the acute inflammatory response. However, the multiple molecular mechanisms through which anaerobic glycolysis and the microtumoral environment are related have not yet been fully elucidated. This article describes the biochemical aspects that show how the PKM2 plays an important role during oncogenesis, especially in the Warburg effect. This represents an adaption mechanism in which, through the alternative splicing, the RNA messenger that encodes for the PKM gene leads to PKM2, a protein that, under hypoxia, mediates an increase in cell viability and proliferation. Finally, the usefulness of PKM2 as a biomarker and possible pharmacological target in some types of cancer is highlighted.