Zonula occludens-1 associated nucleic acid binding protein plays an invasion-promoting role in bladder cancer.

ABSTRACT

Cancer cell invasion is an important characteristic of malignant tumors. Cancer cells overcome the constraints of tight junctions (TJ) to invade other tissues, but less is known about the regulating role of tight junction on bladder cancer (BC) invasion. In order to identify the invasion-regulating function of tight junction component, we investigated the oncogenetic features of zonula occludens-1 associated nucleic acid binding protein (ZONAB), a TJ protein that is usually highly expressed in solid cancers. Expression of ZONAB was found to be up-regulated in human BC cell lines detected by real-time PCR, Western blotting. ZONAB expression was significantly up-regulated in BC cell lines and negatively regulated E-cadherin expression. Overexpression of ZONAB by stable transduction in human BC cell lines promoted invasion detected by transwell invasion assay. Conversely, stable suppression of ZONAB expression by RNA interference (RNAi) in BC cells attenuated invasion. A similar role for ZONAB in promoting invasion and EMT was observed in xenografts. In summary, ZONAB is up-regulated in BC cell lines, which promotes invasion, demonstrating the important role it plays in tumorogenesis and cancer progression.