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

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.

YTHDC1‐dependent m6A modification modulated FOXM1 promotes glycolysis and tumor progression through CENPA in triple‐negative breast cancer

“…CENPA, as the target of FOXM1, has shown the regulation of FOXM1/CENPA in pancreatic β-cell proliferation. 15,45 Here, this study first provides evidence supporting the fact that FOXM1 induced CENPA expression by directly binding to its promoter and subsequently promoted TNBC progression and glycolysis.…”

The role of microfibrillar‐associated protein 2 in cancer

“…It was found that its expression in tumor tissues was significantly higher than that in normal tissues ( 33 ). The MFAP2 mRNA and protein levels in all ovarian cancer cell lines were much higher than those in non-tumor IOSE80 cell lines ( 18 ). In colorectal adenocarcinoma, the MFAP2 mRNA expression in tumor tissues was significantly higher than that in the adjacent non-tumor tissues.…”

“…Similarly, MFAP2 overexpression reduced G1 phase cell proportion and increased those of S and G2/M phase cells in ovarian cancer, suggesting that MFAP2 could stimulate G1-S phase cell transition. In contrast, MFAP2 knockdown induced significant arrest in the G0/G1 phase and decreased the S and G2/M phase cell proportion, indicating that cell cycle processes are affected ( 18 ). These data showed that MFAP2 promotes tumor cell proliferation through numerous mechanisms.…”

“…In contrast, cancer cell energy requirements are increased, and metabolic reprogramming, a cancer cell marker, is critical for tumor growth and metastasis ( 75 ). In ovarian cancer, MFAP2 promotes β-catenin transfer from the cytoplasm to the nucleus via the FoxM1/β-Catenin signal pathway, increasing the glycolysis-related gene (GLUT1 and HK2) expression levels in A2780 and SKOV3 cells ( 18 ).…”

“…Changes in the MFAP2 level regulate ECM remodeling, playing an important role in tumorigenesis ( 32 ). In addition, MFAP2 is important in tumor cell apoptosis, proliferation, angiogenesis, invasion, and prognosis ( 18 , 20 , 23 , 24 ).…”