OLA1 Contributes to Epithelial-mesenchymal Transition in Lung Cancer by Modulating the GSK3β/snail/E-cadherin Signaling

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Feb 11

PMID 26863455

Citations 21

Authors

Li Bai

Zubin Yu

Jiawei Zhang

Shuai Yuan

Chen Liao

Prince V S Jeyabal

Valentina Rubio

Huarong Chen

Yafei Li

Zheng-Zheng Shi

Affiliations

Soon will be listed here.

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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