State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China.
School of Bioengineering, Dalian University of Technology, Dalian, 116024, China.
BMC Mol Cell Biol. 2020 Sep 14;21(1):65. doi: 10.1186/s12860-020-00311-z.
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.
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 TGFβ/SMAD2/EMT pathway.
Our data suggests that OLA1 may be developed as a potential target for the treatment of oral cancer metastasis.
人类 Obg 样 ATP 酶 1（OLA1）蛋白已被报道在癌细胞增殖中发挥重要作用。OLA1 调节口腔转移的分子机制尚不清楚。本研究探讨了 OLA1 在口腔鳞状细胞转移中的调节作用。
通过 RNAi 介导的敲低或过表达进行了一系列体外实验，以阐述 OLA1 在口腔癌中的调节功能。我们发现，高转移性口腔鳞状细胞系中内源性 OLA1 水平明显低于低转移性口腔细胞和正常口腔细胞。OLA1 的过表达导致高转移性细胞的转移能力降低，并使其对紫杉醇治疗的敏感性增加。对 EMT 标志物的进一步分析表明，Snail、Slug、N-钙黏蛋白表达显著上调。同时，OLA1 敲低的口腔癌细胞中 E-钙黏蛋白表达显著下调，表明 OLA1 使 EMT 过程失活。此外，我们发现 OLA1 通过抑制 TGFβ/SMAD2/EMT 通路的活性抑制口腔鳞状细胞转移。
我们的数据表明，OLA1 可能被开发为治疗口腔癌转移的潜在靶点。
