Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFβ/SMAD2 axis in vitro
Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFβ/SMAD2 axis in vitro
复制标题
Obg 样 ATPase 1 通过 TGFβ/SMAD2 轴在体外抑制口腔癌细胞转移。
DOI：
10.1186/s12860-020-00311-z
复制
发表时间：
2020-09-14
影响因子：
2.8
通讯作者：
Xiao, Gary Guishan
中科院分区：
文献类型：
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作者：
Liu, Jianzhou;Yang, Qing;Xiao, Gary Guishan
背景研究发现人OBG样ATP酶1（OLA 1）蛋白在肿瘤细胞增殖中起重要作用。OLA 1调控口腔癌转移的分子机制尚不清楚。本研究旨在探讨OLA 1在口腔鳞状细胞转移中的调控作用。结果通过一系列体外实验，阐明了口腔癌中OLA 1的调控功能。我们发现，内源性水平的OLA 1在高转移性口腔鳞状细胞系显着低于低转移性口腔细胞以及在正常口腔细胞。OLA 1的表达增加导致高转移细胞的转移能力降低，并增强其对紫杉醇治疗的敏感性。EMT标志物分析显示Snail、Slug、N-cadherin表达明显上调。同时，OLA 1基因敲低的口腔癌细胞中E-cadherin表达显著下调，提示OLA 1可抑制EMT过程。此外，我们发现OLA 1通过抑制TGF β/SMAD 2/EMT通路的活性来抑制口腔鳞状细胞转移。结论OLA 1有可能成为治疗口腔癌转移的潜在靶点。
Background The human Obg-like ATPase 1 (OLA1) protein has been reported to play an important role in cancer cell proliferation. The molecular mechanism underlying OLA1 regulated oral metastasis is still unknown. We investigated in this study the regulatory role of OLA1 playing in oral squamous cell metastasis. Results A series of in vitro assays were performed in the cells with RNAi-mediated knockdown or overexpression to expound the regulatory function of OLA1 in oral cancer. We found that the endogenous level of OLA1 in a highly metastatic oral squamous cell line was significantly lower than that in low metastatic oral cells as well as in normal oral cells. Escalated expression of OLA1 resulted in a reduced ability of metastasis in highly metastatic cells, and enhanced its sensitivity to the paclitaxel treatment. Further analysis of the EMT markers showed that Snail, Slug, N-cadherin were up-expressed significantly. Meanwhile, E-cadherin was significantly down-regulated in the oral cancer cells with OLA1-knocked down, suggesting that OLA1 inactivated EMT process. Furthermore, we found that OLA1 suppressed oral squamous cell metastasis by suppressing the activity of a TGF beta/SMAD2/EMT pathway. Conclusion Our data suggests that OLA1 may be developed as a potential target for the treatment of oral cancer metastasis.