DISC1 overexpression promotes non-small cell lung cancer cell proliferation

// Shuo Wang 1, 2, * , Ying-Ying Chen 3, 4, * , Yu-Peng Li 5 , Jun Gu 6 , Shu-Dong Gu 4 , Hai Shi 7 , Xue-Song Li 3 , Xiao-Ning Lu 1, 2 , Xiang Li 8 , Shuang-Long Zhang 1 , Kang-Jun Yu 1 , Kun Liu 1 and Li-Li Ji 2 1 Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China 2 Department of Pathology, Medical School of Nantong University, Nantong, China 3 Department of Immunology, Medical School of Nantong University, Nantong, China 4 Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China 5 Department of Pediatrics, The People’s Hospital of Rizhao, Rizhao, China 6 Department of Respiratory, Affiliated Hospital of Nantong University, Nantong, China 7 Department of Cardiothoracic Surgery, The Third People's Hospital of Nantong, Nantong, China 8 Department of Otorhinolaryngology, Maternal and Child Health Care Hospital of Nantong, Nantong, China * These authors have contributed equally to this work Correspondence to: Kun Liu, email: ntliukun@163.com Li-Li Ji, email: kevin08lily@163.com Keywords: non-small cell lung cancer, DISC1, GSK3β, β-catenin, proliferation Received: February 15, 2017      Accepted: April 27, 2017      Published: May 22, 2017 ABSTRACT 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.