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OLA1 regulates epithelial-mesenchymal transition through the modulation of GSK-3β-Snail-E-cadherin signaling
ZHANG Jiawei 1 * #,BAI Li 2,CHENG Huarong 1,SHI Zhengzheng 1
1.Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310009
2.Department of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037
*Correspondence author
#Submitted by
Subject:
Funding: Specialized Research Fund for the Doctoral Program of Higher Education (No.No. 20110101120123), Zhejiang Provincial Natural Science Foundation of China (No.No. Y2110018)
Opened online:22 December 2015
Accepted by: none
Citation: ZHANG Jiawei,BAI Li,CHENG Huarong.OLA1 regulates epithelial-mesenchymal transition through the modulation of GSK-3β-Snail-E-cadherin signaling[OL]. [22 December 2015] http://en.paper.edu.cn/en_releasepaper/content/4669464
 
 
OLA1 is a member of the Obg family of P-loop NTPases with a putative GTPase-like molecular switch function. In this study the role of OLA1 in the regulation of epithelial-mesenchymal transition (EMT) was characterized in human lung cells and carcinomas. RNAi-mediated silencing of OLA1 rendered both A549 (lung adenocarcinoma-derived) and Beas-2B (noncancerous) cells resistant to transforming growth factor (TGF)-β1-induced transition to mesenchymal morphology accompanied, at molecular level, by reduced loss of epithelial marker E-cadherin and largely demolished Snail, the transcriptional repressor of E-cadherin. Because degradation of Snail is mediated by its phosphorylation by GSK-3, OLA1's effect on GSK-3 was further investigated. OLA1 was found to interact with GSK-3 and be involved in the phosphorylation (Ser9)-mediated GSK-3 deactivation. The protein-protein interaction required the presence of the OLA1 TGS domain, indicating TGS' novel function. These results suggest that OLA1 plays an important role in EMT, especially in lung epithelial cells and tumors, through regulating GSK-3β activity, Snail stability, and expression of E-cadherin.
Keywords:OLA1; EMT; Lung cancer
 
 
 

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