Department of Gynecologic Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Kaohsiung J Med Sci. 2022 Aug;38(8):772-780. doi: 10.1002/kjm2.12546. Epub 2022 May 12.
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.
卵巢癌是一种常见的妇科肿瘤，严重危害着女性的健康和生活质量。微丝相关蛋白 2（MFAP2）已被证明在多种肿瘤的发生发展中发挥着关键作用。然而，MFAP2 在卵巢癌中的功能尚不清楚。在本研究中，我们发现 MFAP2 在卵巢癌细胞和组织中上调，并与 FOXM1 和糖酵解相关基因呈正相关。CCK-8 细胞计数试剂盒、集落形成和流式细胞术检测结果表明，MFAP2 促进了细胞增殖。此外，MFAP2 促进了卵巢癌细胞的增殖、葡萄糖摄取、乳酸生成；增加了细胞内 ATP 水平、细胞外酸化率和耗氧率，并增加了糖酵解蛋白的表达。进一步的机制分析表明，MFAP2 促进了卵巢癌细胞中 FOXM1/β-catenin 介导的糖酵解信号通路。MFAP2 的敲低抑制了卵巢癌异种移植瘤在小鼠中的生长以及 Ki-67、MFAP2、FOXM1、GLUT1、HK2 和β-catenin 的表达。总之，MFAP2 通过调节卵巢癌中的 FOXM1/β-catenin 信号通路促进细胞增殖和糖酵解，这可能为在糖酵解途径中治疗卵巢癌提供新的思路。
