Transmembrane protein 88 (TMEM88) acts as a novel tumor-associated protein. The dysregulation of TMEM88 has been observed in several tumor types. However, the relevance of TMEM88 in tumorigenesis is still contradictory. This study assessed the relevance of TMEM88 in bladder cancer. TMEM88 levels were found to be significantly lower in bladder cancer tissue. Upregulation of TMEM88 resulted in a dramatic decrease in the cellular proliferative and invasive abilities of bladder cancer. Upregulation of TMEM88 decreased the level of active β-catenin and prohibited the activation of the Wnt/β-catenin pathway, an effect that was associated with downregulation of glycogen synthase kinase-3β (GSK-3β) phosphorylation. Suppression of GSK-3β or overexpression of β-catenin reversed the TMEM88-induced tumor-inhibiting effects in bladder cancer. Overexpression of TMEM88 prohibited the tumor formation and growth of bladder cancer cells in nude mice. In conclusion, this study demonstrates that TMEM88 exerts an antitumor function in bladder cancer through downregulation of Wnt/β-catenin signaling.
Keywords: GSK-3β; TMEM88; Wnt; bladder cancer.
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