MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway.
MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway.
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MTHFD2通过激活STAT3信号通路促进卵巢癌生长和转移
DOI：
10.1002/2211-5463.13249
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发表时间：
2021-10
期刊：
影响因子：
2.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Li Q;Yang F;Shi X;Bian S;Shen F;Wu Y;Zhu C;Fu F;Wang J;Zhou J;Chen Y
亚甲基四氢叶酸脱氢酶2（MTHFD 2）是一种位于线粒体中的双功能酶。据报道，MTHFD 2在几种恶性肿瘤中过表达，并与癌症发展有关。本研究旨在研究MTHFD 2对卵巢癌进展的影响。通过生物信息学分析、免疫组织化学、RT-qPCR（真实的-时间定量PCR分析）和蛋白质印迹分析检测MTHFD 2的表达。通过体外实验确定MTHFD 2耗竭对细胞增殖、迁移和侵袭的影响。流式细胞仪检测细胞周期进程和凋亡情况。蛋白质印迹法检测相关信号通路蛋白的表达。我们发现MTHFD 2在卵巢癌组织和细胞系中均高度表达。MTHFD 2缺失抑制细胞增殖和转移。MTHFD 2的敲低可诱导细胞凋亡和G2/M期阻滞，而MTHFD 2过表达可增加S期细胞的数量。在机制上，我们的研究结果表明，MTHFD 2敲低的抑制作用可能是通过下调细胞周期蛋白B1/Cdc 2复合物及其活性的抑制作用介导的。此外，MTHFD 2可以通过激活STAT 3和STAT 3诱导的上皮-间充质转化信号通路来调节细胞生长和侵袭性。这些发现表明MTHFD 2在卵巢癌中过表达，并调节细胞增殖和转移，呈现出有吸引力的治疗靶点。亚甲基四氢叶酸脱氢酶2（MTHFD 2）在卵巢癌组织和细胞系中过表达。MTHFD 2缺失抑制卵巢癌细胞系的细胞生长和转移，并诱导G2/M期阻滞和凋亡。MTHFD 2调节细胞周期蛋白B1/Cdc 2复合物并激活STAT 3和STAT 3诱导的上皮-间充质转化信号通路。总之，我们的结果表明，靶向MTHFD 2可能成为卵巢癌治疗的新方法。
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme located in the mitochondria. MTHFD2 has been reported to be overexpressed in several malignant tumors and is implicated in cancer development. This study aimed to investigate the effect of MTHFD2 on ovarian cancer progression. The expression of MTHFD2 was detected by bioinformatic analysis, immunohistochemistry, RT‐qPCR (real‐time quantitative PCR analysis), and western blot analysis. The effects of MTHFD2 depletion on cell proliferation, migration, and invasion were determined through in vitro experiments. Cell cycle progression and apoptosis were accessed by flow cytometry. The related signaling pathway protein expression was determined by western blot analysis. We found that MTHFD2 is highly expressed in both ovarian cancer tissues and cell lines. MTHFD2 deletion suppressed cell proliferation and metastasis. Knockdown of MTHFD2 induces cell apoptosis and G2/M arrest, whereas the number of cells in S phase increased with MTHFD2 overexpression. Mechanically, our results indicate that an inhibitory effect of MTHFD2 knockdown may be mediated by the downregulation of cyclin B1/Cdc2 complex and the inhibitory effect on its activity. Additionally, MTHFD2 could regulate cell growth and aggressiveness via activation of STAT3 and the STAT3‐induced epithelial–mesenchymal transition signaling pathway. These findings indicate that MTHFD2 is overexpressed in ovarian cancer and regulates cell proliferation and metastasis, presenting an attractive therapeutic target. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is overexpressed in ovarian cancer tissues and cell lines. MTHFD2 depletion inhibits cell growth and metastasis and induces G2/M arrest and apoptosis in ovarian cancer cell lines. MTHFD2 regulates cyclin B1/Cdc2 complex and activates the STAT3 and STAT3‐induced epithelial–mesenchymal transition signaling pathway. Taken together, our results suggest that targeting MTHFD2 maybe served as a novel approach for ovarian cancer treatment.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
8.8
作者：
Newman AC;Maddocks ODK
通讯作者：
Maddocks ODK
影响因子：
50.3
作者：
Martín, A;Odajima, J;Barbacid, M
通讯作者：
Barbacid, M
影响因子：
8
作者：
Green NH;Galvan DL;Badal SS;Chang BH;LeBleu VS;Long J;Jonasch E;Danesh FR
通讯作者：
Danesh FR
DOI：
10.1016/j.biocel.2019.05.011
发表时间：
2019-08-01
影响因子：
4
作者：
Chen, Ming-Jiu;Deng, Jie;Xia, Zhen-Kun
通讯作者：
Xia, Zhen-Kun