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 GSK3 β-interacting protein and inhibits GSK3 β activity by mediating its Ser9 phosphorylation. During EMT, OLA1 plays an important role in suppressing the GSK3 β-mediated degradation of Snail protein, which in turn promotes downregulation of E-cadherin. These data suggest that OLA1 contributes to EMT by modulating the GSK3 β/Snail/E-cadherin signaling, and its overexpression is associated with clinical progression and poor survival in lung cancer patients.
Highlights
Lung cancer is currently the most common cause of cancer-related deaths worldwide
We compared the staining of Obg-like ATPase 1 (OLA1) and E-cadherin among all 110 cancer cases, and found that the OLA1 levels were inversely correlated with the levels of E-cadherin within the same tumor tissue for all histological types of lung cancer (Figure 1A and 1B)
In order to establish the association between OLA1 expression status and overall survival (OS) in patients with lung cancer, we did a meta-analysis of OLA1 expression among 1928 lung cancer patients using the KM plotter software
Summary
Despite advances in diagnosis and treatment, the overall 5-year survival rate of lung cancer remains at about 15% [1]. It can be classified as small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC)—the latter mainly consists of adenocarcinoma and squamous cell carcinoma and represents 85% of lung cancer cases [2]. Epithelial-mesenchymal transition (EMT) is a biological process that enables epithelial cells to acquire mesenchymal phenotypes, including increased migratory and invasive capabilities [3]. A critical molecular event in EMT is the Snail-mediated down-regulation of the epithelial marker E-cadherin, which results in disruption of cellto-cell adhesion and subsequent acquisition of more migratory and invasive phenotype.
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