Jianwei Zhang, Qi Li, Quanquan Xu, Tianen Wang, Qingwei Wang
Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, 450052, China.
Pathol Oncol Res. 2018 Apr;24(2):251-257. doi: 10.1007/s12253-017-0237-z. Epub 2017 May 2.
Transmembrane protease serine 4 (TMPRSS4), a type-II transmembrane serine protease, is involved in the development and progression of wide range of tumors. However, the biological role of TMPRSS4 in prostate cancer remains obscure. Here, we investigated the effect of TMPRSS4 on proliferation and migration in prostate cancer and potential mechanisms. Our findings demonstrated over-expression of TMPRSS4 promoted the PC3 prostate cancer cells migration, which could be reversed by TMPRSS4 silencing. TMPRSS4 induced TWIST1 expression and followed progression of EMT along with upregulation of N-cadherin and downregulation of E-cadherin via STAT3 phosphorylation. Silencing TWIST1 significantly attenuated TMPRSS4-induced PC3 migration. Moreover, knockdown of STAT3 effectively attenuated TMPRSS4-induced TWIST1 expression and TWIST1 promoter activity. Taken together, we demonstrated a mechanistic cascade of TMPRSS4 up-regulating STAT3 activation and subsequent TWIST1 expression, leading to prostate cancer migration.
跨膜蛋白酶丝氨酸4（TMPRSS4）是一种II型跨膜丝氨酸蛋白酶，参与多种肿瘤的发生和发展。然而，TMPRSS4在前列腺癌中的生物学作用仍不清楚。在此，我们研究了TMPRSS4对前列腺癌细胞增殖和迁移的影响及其潜在机制。我们的研究结果表明，TMPRSS4的过表达促进了PC3前列腺癌细胞的迁移，而TMPRSS4沉默可逆转这一现象。TMPRSS4通过STAT3磷酸化诱导TWIST1表达，并随着N-钙黏蛋白的上调和E-钙黏蛋白的下调促进上皮-间质转化（EMT）进程。沉默TWIST1可显著减弱TMPRSS4诱导的PC3细胞迁移。此外，敲低STAT3可有效减弱TMPRSS4诱导的TWIST1表达和TWIST1启动子活性。综上所述，我们证明了TMPRSS4上调STAT3激活并随后诱导TWIST1表达从而导致前列腺癌迁移的机制级联反应。
