PKM2: the thread linking energy metabolism reprogramming with epigenetics in cancer

Abstract

Cancer metabolism reprogramming or alterations in epigenetics are linked to an incidence of cancer. It is apparent that epigenetic changes have been found in tumors, therefore, the complete epigenome and entire pathways relevant to cell metabolism are subject to epigenetic dysregulation. Here, we review the pyruvate kinase M2 (PKM2) isoform, a glycolytic enzyme involved in ATP generation and pyruvate production, which plays an essential role in tumor metabolism and growth, and also functions as a protein kinase that phosphorylates histones during genes transcription and chromatin remodeling. We also discuss the potential role of PKM2 in the dynamic integration between metabolic reprogramming and alterations in epigenetics during carcinogenesis and cancer progression.

Figure 1

A hypothetic model illustrates the functional role of nuclear PKM2 (pyruvate kinase M2) in epigenetics and cancer cell metabolism.PKM2 can translocateinto nucleus and phosphorylate H1, H3, and STAT3 for its protein kinase activity. Furthermore, the interaction of PKM2 with prolyl hydroxylase 3 (PHD3) as well as hypoxia-inducible factor 1α (HIF1α) induces glycolytic gene expression; the intact comblex of PKM2 and β-catenin is required for cyclin D1 expression and activation of c-Myc transcription. The interaction of jumonji C domain-containing 5 (JMJD5) with PKM2 initiates HIF1α transcription by blocking its protein kinase activity.