Epithelial-mesenchymal transition; Metastasis; Non-small cell lung cancer; Snail; ZIP4; Oncology; Cancer Research
Abstract :
[en] Non-small cell lung cancer (NSCLC) is one of the most critical health problems worldwide, with high incidence and poor survival rate. A zinc importer ZIP4 has been implicated in the process of tumor growth and metastasis of many cancers. However, its exact role and the underlying mechanism in NSCLC remains to be elucidated. In the present study, we found that human ZIP4 was substantially overexpressed in NSCLC tissues and was correlated with poor overall survival (OS) and progression-free survival (PFS). Overexpression of ZIP4 promoted cell migration, invasion and metastasis both in vitro and in a mouse lung metastasis model. Silencing of ZIP4 attenuated migration, invasion and metastasis. Mechanistically, overexpression of ZIP4 increased the expression of Snail, Slug and N-cadherin while genetic inactivation of ZIP4 downregulated the expression of above-mentioned genes. Further analysis showed that transcriptional factor Snail which modulates N-cadherin was involved in the process of ZIP4-mediated NSCLC migration and invasion. We also demonstrated that ZIP4 positively correlates with the levels of Snail, Slug and N-cadherin in mice lung metastasis tumors. Together, these results suggest that ZIP4 acts as an important regulator of Snail-N-cadherin signaling axis in promoting NSCLC progression and may serve as a novel predictive marker and therapeutic target in NSCLC.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Jiang, Yuanyuan; Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, Shandong, China, Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Zhan, Hanxiang; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
Zhang, Yuqing; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Yang, Jingxuan ; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Liu, Mingyang; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Xu, Chao ; Department of Biostatistics and Epidemiology, Hudson College of Public Health, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Fan, Xiao ; Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Zhang, Junxia; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Zhou, Zhijun ; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Shi, Xiuhui ; Université de Liège - ULiège > Département de pharmacie ; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Ramesh, Rajagopal; Department of Pathology, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Li, Min; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA, Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: Min-Li@ouhsc.edu
Language :
English
Title :
ZIP4 promotes non-small cell lung cancer metastasis by activating snail-N-cadherin signaling axis.
This work was partially supported by the Department of Medicine at OUHSC. We thank the Stephenson Cancer Center at OUHSC for the use of the Biostatistics Core and Small Animal Bioluminescent Imaging Core facilities.This work was partially supported by the Department of Medicine at OUHSC . We thank the Stephenson Cancer Center at OUHSC for the use of the Biostatistics Core and Small Animal Bioluminescent Imaging Core facilities.
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