癌症研究
信号转导
上皮-间质转换
肺癌
整合素连接激酶
细胞生长
转移
激酶
生物
化学
癌症
医学
肿瘤科
细胞生物学
蛋白激酶A
内科学
生物化学
细胞周期蛋白依赖激酶2
作者
Feng Zhou,Ziyi Yuan,Yuyan Gong,Luyao Li,Yanmao Wang,Xian Wang,Chunbo Ma,Lehe Yang,Zhiguo Liu,Liangxing Wang,Haiyang Zhao,Chengguang Zhao,Xiaoying Huang
标识
DOI:10.1016/j.biopha.2023.114412
摘要
Lung cancer is the most common cause of cancer related deaths worldwide with the highest mortality rate. Non-small cell lung cancer (NSCLC) accounts for about 85 % of lung cancers. Mitochondrial methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme and is the most differentially expressed metabolic enzyme in various tumors including lung cancer. However, little is known about how MTHFD2 functions in NSCLC. Integrin-linked kinase (ILK) signaling plays key a role in tumor progression including metastasis, proliferation and migration. Here, we show that MTHFD2 inhibition results in suppression of cell growth, migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC. Microarray analysis suggests that MTHFD2 is positively associated with ILK signaling based on western blotting results. In addition, the phosphorylation of AMPKα plays an essential role in MTHFD2 regulation of ILK signaling. Further, the small-molecule compound C18 inhibits MTHFD2 with great efficiency. C18 blocks MTHFD2/ILK signaling pathway and restrains cell growth, migration, invasion, and EMT of NSCLC and induces apoptosis. In brief, our study found that the positive impact of MTHFD2 is mediated via ILK signaling pathway in NSCLC. Thus, blocking MTHFD2 represents a promising therapeutic strategy against NSCLC clinically.
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