Introduction Endometrial cancer (EC) is one of the most common malignant tumors in the female reproductive system. The incidence and mortality of EC have been increasing in the past 40 years.As an important member of the insulin-like growth factor (IGF) family, IGF binding protein 2 (IGFBP2) is an important molecular target in many cancers, also plays a pivotal role in metabolic diseases, such as obesity and diabetes. However, whether IGFBP2 in EC can affect the metabolism of tumor cells and participate in the metabolic reprogramming of endometrial adenocarcinoma cells and consequently affect tumorigenesis and progression, these questions are still unclear and the specific mechanisms have not been elucidated.

Methods Cancer and paracancer tissue specimens were collected from 80 patients with EC, and the expression of IGFBP2, PKM2 and glycolytic enzymes in the tissues were examined. The expression of IGFBP2 in EC cells was altered to detect the effect of IGFBP2 on cellular glycolysis, and the expression of key enzymes of intracellular glycolysis was examined.

Results IGFBP2 and PKM2 were highly expressed in tumor tissues of EC patients and correlated with tumor stage and differentiation. After knockdown of IGFBP2 expression in EC cells, cell proliferation capacity was significantly reduced, tumorigenic capacity in vivo was decreased, cellular glycolytic function, glucose uptake, lactate production and ATP production were significantly reduced, the expression levels of various key enzymes of glucose metabolism were significantly reduced, and the nuclear plasma ratio of PKM2 was decreased.

Conclusion/Implications We found IGFBP2 regulates glucose metabolism reprogramming through PKM2 to promote endometrial adenocarcinoma progression.