MFAP2 aggravates tumor progression through activating FOXM1/β‐catenin‐mediated glycolysis in ovarian cancer

Abstract

Abstract Ovarian cancer is one of the most common gynecological tumors that seriously endanger the health and quality of life of women. Microfibril‐associated protein 2 (MFAP2) has been demonstrated to play crucial roles in the development of multiple tumors. However, the function of MFAP2 in ovarian cancer remains unclear. In this study, we found that MFAP2 was upregulated in ovarian cancer and cells and was positively correlated with FOXM1 and glycolysis‐related genes. The results of Cell Count Kit‐8, colony formation, and flow cytometry assays indicated that MFAP2 promoted cell proliferation. In addition, MFAP2 promotes cell proliferation, glucose uptake, lactate production; increases ATP levels, extracellular acidification ratio, and oxygen consumption ratio in ovarian cancer cells and increases the expression of glycolytic proteins. Further mechanistic analysis suggests that MFAP2 promotes FOXM1/β‐catenin‐mediated glycolysis signaling in ovarian cancer cells. Knockdown of MFAP2 inhibits ovarian cancer xenograft tumor growth and expression of Ki‐67, MFAP2, FOXM1, GLUT1, HK2, and β‐catenin in mice. In conclusion, MFAP2 promotes cell proliferation and glycolysis by modulating the FOXM1/β‐catenin signaling pathway in ovarian cancer, which may offer a fresh insight into the treatment of ovarian cancer in the glycolysis pathway.

Keywords

• CCK‐8
• FOXM1
• GLUT1
• microfibril‐associated protein 2 (MFAP2)
• ovarian cancer