Sperm-associated antigen 4 (SPAG4) as a new cancer marker interacts with Nesprin3 to regulate cell migration in lung carcinoma

Lung cancer is the most common cause of cancer-related deaths, and early diagnosis and targeted therapy are extremely important in the treatment of this disease. Sperm-associated antigen 4 (SPAG4) was recently found to be a novel cancer biomarker. In the present study, the expression of SPAG4 was revealed to be high in lung adenocarcinoma tissues as determined by western blotting and immunohistochemistry. SPAG4 knockdown by RNAi efficiently reduced the migration of the lung cancer A549 cells in vitro. Mechanistically, SPAG4 exerted its tumor promoting functions by interacting with Nesprin3 as determined by co-immunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) techniques. In addition, immunofluorescence revealed that the level of SPAG4 in lung cancer cells could affect the location and expression of Nesprin3. Furthermore, silencing of Nesprin3 reduced the migration of A549 cells and we provided evidence to demonstrate that SPAG4 acted as a positive regulator of Nesprin3. The results revealed that SPAG4, in cooperation with Nesprin3, has a fundamental pathological function in the migration of lung carcinoma cells, and the SPAG4 gene may be useful for the clinical diagnosis and new treatment strategies in patients with lung cancer.