PKM2 and cancer: The function of PKM2 beyond glycolysis

TLDR

Metabolic reprogramming is a hallmark of cancer, with PKM2—a key glycolytic enzyme—playing a central role in tumor metabolism and growth. This review investigates PKM2’s expression, regulation, metabolic and non‑metabolic functions, and evaluates its potential as a therapeutic target. PKM2 functions as a limiting enzyme in glycolysis while also acting as a coactivator and protein kinase to meet the nutrient demands of proliferating cancer cells. A deeper understanding of PKM2 may offer a novel approach for cancer treatment.

Abstract

Metabolic reprogramming is a hallmark of cancer cells and is used by cancer cells for growth and survival. Pyruvate kinase muscle isozyme M2 (PKM2) is a limiting glycolytic enzyme that catalyzes the final step in glycolysis, which is key in tumor metabolism and growth. The present review discusses the expression and regulation of PKM2, and reports the dominant role that PKM2 plays in glycolysis to achieve the nutrient demands of cancer cell proliferation. In addition, the present study discusses the non-metabolic function of PKM2, and its role as a coactivator and protein kinase, which contributes to tumorigenesis. Furthermore, conflicting studies concerning the role of PKM2 as a therapeutic target are reviewed. The improved understanding of PKM2 may provide a noval approach for cancer treatment.