Gil Dorota, Ciołczyk-Wierzbicka Dorota, Dulińska-Litewka Joanna, Laidler Piotr
Chair of Medical Biochemistry, Jagiellonian University Medical College, ul.Kopernika 7, 31-034, Kraków, Poland.
Tumour Biol. 2016 Nov;37(11):15185-15191. doi: 10.1007/s13277-016-5354-x. Epub 2016 Sep 28.
Cadherin switch is specific of epithelial-mesenchymal transition (EMT) and is closely related to tumor cell invasion. However, the molecular mechanism that promotes the phenotypic changes remains unclear and elusive. We found that integrin-linked kinase (ILK) is a key factor involved in cadherin switch. The expression and activity of ILK are elevated in a variety of cancers but its mechanisms are not exactly understood. In this report, we studied the role and mechanism of ILK in EMT of human bladder cancer. We showed that silencing of ILK expression by small interfering RNA (siRNA) significantly abolished the nuclear translocation or the presence of markers associated with EMT like Snail, Twist, Zeb, and beta-catenin. ILK knockdown by siRNA suppressed N-cadherin expression and increased re-expression of E-cadherin in bladder cancer cells. We suggest that ILK is a major signaling factor involved in EMT. It is essential to understand the molecular mechanism of EMT in aim to possibly use it in search for new therapeutic targets.
钙黏蛋白转换是上皮-间质转化(EMT)所特有的,且与肿瘤细胞侵袭密切相关。然而,促进表型变化的分子机制仍不清楚且难以捉摸。我们发现整合素连接激酶(ILK)是参与钙黏蛋白转换的关键因素。ILK的表达和活性在多种癌症中均升高,但其机制尚未完全明确。在本报告中,我们研究了ILK在人膀胱癌EMT中的作用及机制。我们发现,通过小干扰RNA(siRNA)沉默ILK表达可显著消除与EMT相关标志物(如Snail、Twist、Zeb和β-连环蛋白)的核转位或存在。通过siRNA敲低ILK可抑制膀胱癌细胞中N-钙黏蛋白的表达并增加E-钙黏蛋白的重新表达。我们认为ILK是参与EMT的主要信号因子。为了有可能将其用于寻找新的治疗靶点,了解EMT的分子机制至关重要。