Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFβ/SMAD2 axis in vitro

BMC Molecular and Cell Biology

Thomas Dobleman¹  Kevin Chen Xiao²  Shen Hu²  Qing Yang³  Jianzhou Liu⁴  Gary Guishan Xiao⁵ 

[1] Functional Genomics and Proteomics Center, Creighton University Medical Center, 68131, Omaha, USA;School of Dentistry, University of California Los Angeles, 90095, Los Angeles, USA;State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 116024, Dalian, China;State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 116024, Dalian, China;School of Bioengineering, Dalian University of Technology, 116024, Dalian, China;State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Sciences, School of Chemical Engineering, Dalian University of Technology, 116024, Dalian, China;School of Bioengineering, Dalian University of Technology, 116024, Dalian, China;Functional Genomics and Proteomics Center, Creighton University Medical Center, 68131, Omaha, USA;

关键词: Metastasis;    OLA1;    EMT;    Oral squamous cell carcinoma;    SMAD2;   

DOI  :  10.1186/s12860-020-00311-z

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsA 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.ConclusionOur data suggests that OLA1 may be developed as a potential target for the treatment of oral cancer metastasis.

【 授权许可】

CC BY