Pyruvate kinase M2 (PKM2) is a pivotal enzyme in glycolysis, catalyzing the conversion of phosphoenolpyruvate (PEP) into pyruvate while generating ATP through substrate-level phosphorylation. Unlike other pyruvate kinase isoforms, PKM2 exhibits unique regulatory properties that allow it to switch between active tetrameric and less-active dimeric states, influencing both energy metabolism and biosynthetic pathways. PKM2 is widely expressed in tumors, where it plays a central role in metabolic reprogramming and cancer progression. Beyond its metabolic function, recent studies have identified non-canonical roles for PKM2, including its nuclear translocation and protein kinase activity, which influence gene expression, cell cycle regulation, and tumor proliferation. The Warburg effect, characterized by enhanced glycolysis in cancer cells despite oxygen availability, is often mediated by PKM2. Oncogene-driven PKM2 modulation contributes to tumor survival, metastasis, and resistance to therapy. Its overexpression in multiple cancers, including breast, prostate, lung, colorectal, and liver malignancies, makes PKM2 a promising target for therapeutic intervention. Natural and synthetic PKM2 inhibitors have shown potential in preclinical studies, demonstrating anti-tumor efficacy by altering metabolic flux and disrupting cancer cell growth. This review explores PKM2’s dual role in metabolism and oncogenic signaling, emphasizing its impact on tumorigenesis and therapeutic targeting. Further research is needed to optimize PKM2-targeted strategies, paving the way for improved cancer treatments.
Natasha Ali (Fri,) studied this question.