The dual-faced pyruvate kinase M2 in tumors: From cytoplasmic metabolic gatekeeper to nuclear transcriptional coactivator

The Warburg effect is a key hallmark of abnormal energy metabolism in tumor cells. As a key rate-limiting enzyme in the terminal step of glycolysis, pyruvate kinase plays a pivotal role in regulating tumor metabolic reprogramming. Among the four tissue-specific isoforms of pyruvate kinase in mammals, pyruvate kinase M2 (PKM2) stands out due to its preferential expression in tumor cells. This review summarizes the structural characteristics of PKM2, including its domain composition and oligomeric assembly patterns. Subsequently, it elaborates on the dual biological functions and post-translational modifications of PKM2, as well as the specific roles of PKM2 in tumorigenesis and progression. Finally, the research advances in PKM2 inhibitors and activators are summarized based on their distinct action mechanisms. This work aims to provide a comprehensive reference for understanding the biological roles of PKM2 in tumors and to facilitate the translation of PKM2-targeted tumor therapeutic strategies into clinical practice.