Regulatory mechanisms of PFKFB2 in glycolysis and tumor metabolism: implications for cancer therapy

Glycolysis is a crucial metabolic process that facilitates the rapid proliferation of cancer cells. Phosphofructokinase-1 (PFK-1) is the key rate-limiting enzyme in glycolysis, with fructose-2,6-diphosphate (F-2,6-BP) acting as its most effective regulator. The levels of F-2,6-BP are closely correlated with the activity of 6-phosphate fructose-2-kinase/fructose-2,6-diphosphatase (PFK-2/FBPase-2, PFKFB). The PFKFB family consists of four isoenzymes: PFKFB1-4. Most evidence suggests that PFKFB activity is essential for activating glycolytic and oncogenic properties in tumor cells. However, previous studies have focused predominantly on PFKFB3 and PFKFB4, with relatively few investigating PFKFB2. The role of PFKFB2 in cancer is complex and multifaceted, encompassing various aspects of tumor metabolism, cell migration, invasion, and the immune response. Consequently, this review aims to summarize the current understanding of the gene structure and biological function of PFKFB2 and to explore its pathogenic mechanisms in different cancers. Additionally, we highlight the metabolic signaling pathways associated with PFKFB2. This review seeks to provide insights into the current status of PFKFB2 and to assist in identifying new targets for cancer therapy.