Shi Lin, Liu Huize, Wang Yifeng, Chong Yulong, Wang Jie, Liu Guanzheng, Zhang Xu, Chen Xiangyu, Li Huan, Niu Mingshan, Liang Jun, Yu Rutong, Liu Xuejiao
1Institute of Nervous System Diseases, Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu China.
Nanjing Durm Tower Hospital Group, Suqian City People's Hospital, Suqian, Jiangsu China.
Cancer Cell Int. 2019 Nov 21;19:305. doi: 10.1186/s12935-019-1035-3. eCollection 2019.
Switch-associated protein 70 (SWAP-70) is a guanine nucleotide exchange factor that is involved in cytoskeletal rearrangement and regulation of migration and invasion of malignant tumors. However, the mechanism by which SWAP-70 regulates the migration and invasion of glioblastoma (GB) cells has not been fully elucidated.
This study used an online database to analyze the relationship between SWAP-70 expression and prognosis in GB patients. The in vitro wound healing assay and transwell invasion assay were used to determine the role of SWAP-70 in GB cell migration and invasion as well as the underlying mechanism.
We found that patients with high SWAP-70 expression in the GB had a poor prognosis. Downregulation of SWAP-70 inhibited GB cell migration and invasion, whereas SWAP-70 overexpression had an opposite effect. Interestingly, SWAP-70 expression was positively correlated with the expression of the standard form of CD44 (CD44s) in GB tissues. Downregulation of SWAP-70 also reduced CD44s protein expression, whereas SWAP-70 overexpression enhanced CD44s protein expression. However, downregulation of SWAP-70 expression did not affect the mRNA expression of CD44s. Reversal experiments showed that overexpressing CD44s in cell lines with downregulated SWAP-70 partially abolished the inhibitory effects of downregulated SWAP-70 on GB cell migration and invasion.
These results suggest that SWAP-70 may promote GB cell migration and invasion by regulating the expression of CD44s. SWAP-70 may serve as a new biomarker and a potential therapeutic target for GB.
开关相关蛋白70(SWAP-70)是一种鸟嘌呤核苷酸交换因子,参与细胞骨架重排以及恶性肿瘤迁移和侵袭的调控。然而,SWAP-70调节胶质母细胞瘤(GB)细胞迁移和侵袭的机制尚未完全阐明。
本研究使用在线数据库分析GB患者中SWAP-70表达与预后的关系。采用体外伤口愈合试验和Transwell侵袭试验来确定SWAP-70在GB细胞迁移和侵袭中的作用及其潜在机制。
我们发现GB中SWAP-70高表达的患者预后较差。SWAP-70的下调抑制了GB细胞的迁移和侵袭,而SWAP-70的过表达则产生相反的效果。有趣的是,SWAP-70的表达与GB组织中标准形式的CD44(CD44s)的表达呈正相关。SWAP-70的下调也降低了CD44s蛋白的表达,而SWAP-70的过表达则增强了CD44s蛋白的表达。然而,SWAP-70表达的下调并不影响CD44s的mRNA表达。逆转实验表明,在SWAP-70下调的细胞系中过表达CD44s部分消除了SWAP-70下调对GB细胞迁移和侵袭的抑制作用。
这些结果表明,SWAP-70可能通过调节CD44s的表达来促进GB细胞的迁移和侵袭。SWAP-70可能作为GB的一种新的生物标志物和潜在的治疗靶点。