DISC1 overexpression promotes non-small cell lung cancer cell proliferation
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Shuo Wang1,2,*, Ying-Ying Chen3,4,*, Yu-Peng Li5, Jun Gu6, Shu-Dong Gu4, Hai Shi7, Xue-Song Li3, Xiao-Ning Lu1,2, Xiang Li8, Shuang-Long Zhang1, Kang-Jun Yu1, Kun Liu1 and Li-Li Ji2
1Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China
2Department of Pathology, Medical School of Nantong University, Nantong, China
3Department of Immunology, Medical School of Nantong University, Nantong, China
4Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China
5Department of Pediatrics, The People’s Hospital of Rizhao, Rizhao, China
6Department of Respiratory, Affiliated Hospital of Nantong University, Nantong, China
7Department of Cardiothoracic Surgery, The Third People's Hospital of Nantong, Nantong, China
8Department of Otorhinolaryngology, Maternal and Child Health Care Hospital of Nantong, Nantong, China
*These authors have contributed equally to this work
Kun Liu, email: [email protected]
Li-Li Ji, email: [email protected]
Keywords: non-small cell lung cancer, DISC1, GSK3β, β-catenin, proliferation
Received: February 15, 2017 Accepted: April 27, 2017 Published: May 22, 2017
Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/β-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and may promote neural progenitor cell and pancreatic β-cell proliferation. The present study found that DISC1 promotes non-small cell lung cancer (NSCLC) cell growth. Western blotting and immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC cell lines and patient tissues. DISC1 expression was negatively associated with phosphorylated (p-) GSK3β, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis. siRNA-mediated DISC1 silencing increased p-GSK3β expression and decreased expression of β-catenin and Cyclin D1, while DISC1 upregulation produced the opposite results. DISC1 knockdown also reduced NSCLC cell proliferation rates in vitro. These results suggest that DISC1 promotes NSCLC growth, likely through GSK3β/β-catenin signaling, and that DISC1 may function as an oncogene and novel anti-NSCLC therapeutic target.
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