Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Medical Department, Xi'an Daxing Hospital, Xi'an, Shaanxi, People's Republic of China.
J Biochem Mol Toxicol. 2021 Aug;35(8):e22835. doi: 10.1002/jbt.22835. Epub 2021 May 31.
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.
跨膜蛋白 88（TMEM88）作为一种新型肿瘤相关蛋白发挥作用。在几种肿瘤类型中观察到 TMEM88 的失调。然而，TMEM88 在肿瘤发生中的相关性仍然存在争议。本研究评估了 TMEM88 在膀胱癌中的相关性。发现膀胱癌组织中 TMEM88 的水平显著降低。TMEM88 的上调导致膀胱癌细胞的增殖和侵袭能力显著下降。TMEM88 的上调降低了活性 β-连环蛋白的水平，并抑制了 Wnt/β-连环蛋白通路的激活，这种作用与糖原合酶激酶-3β（GSK-3β）磷酸化的下调有关。GSK-3β 的抑制或 β-连环蛋白的过表达逆转了 TMEM88 对膀胱癌的抑制作用。TMEM88 的过表达抑制了裸鼠膀胱癌细胞的肿瘤形成和生长。总之，本研究表明 TMEM88 通过下调 Wnt/β-连环蛋白信号通路在膀胱癌中发挥抗肿瘤作用。
