Dual roles of PKM2 in cancer metabolism

Abstract

Cancer cells have distinct metabolism that highly depends on glycolysis instead of mitochondrial oxidative phosphorylation alone, known as aerobic glycolysis. Pyruvate kinase (PK), which catalyzes the final step of glycolysis, has emerged as a potential regulator of this metabolic phenotype. Expression of PK type M2 (PKM2) is increased and facilitates lactate production in cancer cells, which determines whether the glucose carbons are degraded to pyruvate and lactate or are channeled into synthetic processes. Modulation of PKM2 catalytic activity also regulates the synthesis of DNA and lipids that are required for cell proliferation. However, the mechanisms by which PKM2 coordinates high-energy requirements with high anabolic activities to support cancer cell proliferation are still not completely understood. This review summarizes the biological characteristics of PKM2 and discusses the dual role in cancer metabolism as well as the potential therapeutic applications. Given its pleiotropic effects on cancer biology, PKM2 represents an attractive target for cancer therapy.

Pyruvate Kinase M2 Regulates Hif-1α Activity and IL-1β Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages

“…The pyruvate kinase activity of the tetramers can be regulated by the concentration of the naturally occurring upstream glycolytic intermediate FBP (Ashizawa et al, 1991; Jurica et al, 1998), serine (Chaneton et al, 2012), as well as by a multitude of post-translational modifications (Wu and Le, 2013) including tyrosine phosphorylation. Activity is controlled by stabilizing or destabilizing the tetramer (Hitosugi et al, 2009).…”

Tumor glycolysis as a target for cancer therapy: progress and prospects

“…Next, PK-M2 is involved in the regulation of macromolecular biosynthesis (e.g. nucleic acid) [48] and multiple reports have established its role in tumor progression [49-51]. In addition to its involvement in biosynthesis, nuclear translocation of its phosphorylated form has been shown to promote the Warburg effect [52].…”

Potential diagnostic and prognostic marker dimethylglycine dehydrogenase (DMGDH) suppresses hepatocellular carcinoma metastasis in vitro and in vivo

“…Recently, alteration of important enzymes involved in glucose metabolism including somatic mutation of IDH1/2 in have been reported in HCC patients [6]. In breast cancer, over-expression of PKM2 leads to glucose fluxes into the pentose phosphate pathway (PPP) instead of glycolysis [7], and produce more ribose, which is one of the most important architectural components of DNA and RNA. In HCC, glutaminase 2 was reported to regulate PI3K/AKT signaling pathway and suppress tumor activity [8].…”