Oncotarget

Research Papers:

OLA1 contributes to epithelial-mesenchymal transition in lung cancer by modulating the GSK3β/snail/E-cadherin signaling

Li Bai, Zubin Yu, Jiawei Zhang, Shuai Yuan, Chen Liao, Prince V.S. Jeyabal, Valentina Rubio, Huarong Chen, Yafei Li and Zheng-Zheng Shi _

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Oncotarget. 2016; 7:10402-10413. https://doi.org/10.18632/oncotarget.7224

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Abstract

Li Bai1,2,*, Zubin Yu3,*, Jiawei Zhang4, Shuai Yuan5, Chen Liao1, Prince V.S. Jeyabal2, Valentina Rubio2, Huarong Chen2,4, Yafei Li5,** and Zheng-Zheng Shi2,**

1 Department of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, China

2 Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas, USA

3 Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China

4 Cancer Institute, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

5 Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China

* These authors have contributed equally to this work

** These authors jointly directed the project

Correspondence to:

Yafei Li, email:

Zheng-Zheng Shi, email:

Keywords: Obg-like ATPase 1, epithelial-mesenchymal transition, GSK3β, E-cadherin, lung cancer

Received: September 19, 2015 Accepted: January 24, 2016 Published: February 06, 2016

Abstract

Obg-like ATPase 1 (OLA1) belongs to the Obg family of P-loop NTPases, and may serve as a “molecular switch” regulating multiple cellular processes. Aberrant expression of OLA1 has been observed in several human malignancies. However, the role of OLA1 in cancer progression remains poorly understood. In this study, we used the Kaplan-Meier plotter search tool to show that increased expression of OLA1 mRNA was significantly associated with shorter overall survival in lung cancer patients. By immunohistochemical analysis we discovered that levels of OLA1 protein in lung cancer tissues were positively correlated with TNM stage and lymph node metastasis, but negatively correlated with the epithelial-mesenchymal transition (EMT) marker E-cadherin. Knockdown of OLA1 in a lung adenocarcinoma cell line rendered the cells more resistant to TGF-β-induced EMT and the accompanied repression of E-cadherin. Furthermore, our results demonstrated that OLA1 is a GSK3β-interacting protein and inhibits GSK3β activity by mediating its Ser9 phosphorylation. During EMT, OLA1 plays an important role in suppressing the GSK3β-mediated degradation of Snail protein, which in turn promotes downregulation of E-cadherin. These data suggest that OLA1 contributes to EMT by modulating the GSK3β/Snail/E-cadherin signaling, and its overexpression is associated with clinical progression and poor survival in lung cancer patients.


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