Disc1 Overexpression Promotes Non-Small Cell Lung Cancer Cell Proliferation

Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/beta-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3 beta) phosphorylation, and may promote neural progenitor cell and pancreatic beta-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-) GSK3 beta, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis. siRNA-mediated DISC1 silencing increased p-GSK3 beta expression and decreased expression of beta-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 GSK3 beta/beta-catenin signaling, and that DISC1 may function as an oncogene and novel anti-NSCLC therapeutic target.