Pgk1, or phosphoglycerate kinase 1, is an essential enzyme in the aerobic glycolysis pathway. It catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate to ADP, producing 3-phosphoglycerate and ATP. Besides its role in cell metabolism regulation, Pgk1 is involved in multiple biological activities such as angiogenesis, autophagy, and DNA repair [3].

Many studies have focused on Pgk1's role in cancer. Hypoxia-induced downregulation of Pgk1 crotonylation at K131, K156, and K220 promotes tumorigenesis by coordinating glycolysis and the TCA cycle [1]. O-GlcNAcylation at T255 activates Pgk1 activity, enhancing lactate production and inducing its translocation into mitochondria where it inhibits the pyruvate dehydrogenase complex, promoting tumor growth [2]. Macrophage-associated Pgk1 phosphorylation at T243 by PDPK1, facilitated by macrophage-secreted IL-6, promotes aerobic glycolysis and tumorigenesis in tumor cells [4]. Also, in SMAD4-negative pancreatic cancer, loss of SMAD4 induces Pgk1 upregulation. Nuclear Pgk1 drives cell metastasis via mitochondrial oxidative phosphorylation, while cytoplasmic Pgk1 supports proliferation as a glycolytic enzyme [5].

In conclusion, Pgk1 plays a crucial role in coordinating glycolysis and the TCA cycle, which is instrumental in cancer metabolism and tumorigenesis. These findings from various studies, though not all from KO/CKO mouse models, help us understand the role of Pgk1 in cancer development, potentially providing new therapeutic targets for cancer treatment.