title: OLA1 contributes to epithelial-mesenchymal transition in lung cancer by modulating the GSK3β/snail/E-cadherin signaling.
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.
authors: Department of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, China.|Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas, USA.
authors: Li
authors: L
authors: Bai
authors: Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Zubin
authors: Z
authors: Yu
authors: Cancer Institute, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Jiawei
authors: J
authors: Zhang
authors: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors: Shuai
authors: S
authors: Yuan
authors: Department of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Chen
authors: C
authors: Liao
authors: Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas, USA.
authors: Prince V S
authors: PV
authors: Jeyabal
authors: Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas, USA.
authors: Valentina
authors: V
authors: Rubio
authors: Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas, USA.|Cancer Institute, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Huarong
authors: H
authors: Chen
authors: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors: Yafei
authors: Y
authors: Li
authors: Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas, USA.
authors: Zheng-Zheng
authors: ZZ
authors: Shi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D010766:Phosphorylation; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D053773:Transforming Growth Factor beta1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; C522732:OLA1 protein, human
keywords: E-cadherin; GSK3β; Obg-like ATPase 1; epithelial-mesenchymal transition; lung cancer