Suppression of SIPA-1 expression may reduce bladder cancer invasion and metastasis via the downregulation of E-cadherin and ZO-1.

The aim of the present study was to investigate the capacity of signal-induced proliferation-associated protein 1 (SIPA-1) to regulate bladder cancer cell invasion and metastasis. BIU-87 and T24 cells were transfected with the SIPA gene and SIPA short hairpin (sh)RNA, respectively. Western blot analysis was conducted to analyze the expression levels of SIPA-1, Ras-related protein 1 (Rap1), Rap1 guanosine triphosphate (Rap1GTP), E-cadherin and zona occludens-1 (ZO-1). Cell motility and invasion were evaluated in vitro using wound and Transwell assays. Transfected cells were inoculated into the pelvic region of BALB/c nude mice, and the number of resulting tumors was recorded after 6 weeks. Western blot analysis revealed that expression levels of E-cadherin and ZO-1 were reduced in the cells with enhanced levels of SIPA-1. By contrast, the levels of E-cadherin and ZO-1 were elevated in the cells in which SIPA-1 was knocked down. In comparison with untransfected cells, the cells with reduced levels of SIPA-1 exhibited reduced wound closure and fewer cells crossed the chamber in the Transwell experiment, whereas the cells with enhanced levels of SIPA-1 exhibited increased migration and invasion In vivo, an increased tumor count was obtained in the mice with elevated levels of SIPA-1. Therefore, the results of the present study indicate that SIPA-1 is able to regulate bladder cancer cell metastasis and invasion by reducing the expression of E-cadherin and ZO-1.