胰岛素样生长因子-1通过信号转导子和转录激活子5在肝细胞癌中诱导上皮-间质转化。

IGF-1 induces the epithelial-mesenchymal transition via Stat5 in hepatocellular carcinoma.

作者信息

Zhao Chuanzong, Wang Qian, Wang Ben, Sun Qi, He Zhaobin, Hong Jianguo, Kuehn Florian, Liu Enyu, Zhang Zongli

机构信息

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, P.R. China.

Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China.

出版信息

Oncotarget. 2017 Dec 5;8(67):111922-111930. doi: 10.18632/oncotarget.22952. eCollection 2017 Dec 19.

It has been reported that the epithelial-mesenchymal transition (EMT) plays an important role in hepatocellular carcinoma (HCC). However, the relationship between the insulin-like growth factor-1 (IGF-1) and EMT of HCC was not fully elucidated. In the present work, we found that the expression of N-cadherin, Vimentin, Snail1, Snail2, and Twist1 was positively associated with IGF-1R expression, while E-cadherin expression was negatively associated with IGF-1 expression in human HCC samples. Furthermore, we observed that IGF-1 up-regulated the expression of N-cadherin, Vimentin, Snail1, Snail2 and Twist1, and down-regulated the expression of E-cadherin. In addition, Stat5 was induced in IGF-1-treated HepG2 and Hep3B cells, and Stat5 inhibition or siRNA significantly affected IGF-1-induced EMT in HepG2 and Hep3B cells. In conclusion, IGF-1 induces EMT of HCC via Stat5 signaling pathway. Thus, IGF-1/Stat5 can be recommended as a potential and novel therapeutic strategy for HCC patients.

据报道，上皮-间质转化（EMT）在肝细胞癌（HCC）中起重要作用。然而，胰岛素样生长因子-1（IGF-1）与HCC的EMT之间的关系尚未完全阐明。在本研究中，我们发现，在人HCC样本中，N-钙黏蛋白、波形蛋白、Snail1、Snail2和Twist1的表达与IGF-1R表达呈正相关，而E-钙黏蛋白表达与IGF-1表达呈负相关。此外，我们观察到IGF-1上调N-钙黏蛋白、波形蛋白、Snail1、Snail2和Twist1的表达，并下调E-钙黏蛋白的表达。另外，在IGF-1处理的HepG2和Hep3B细胞中诱导了Stat5，Stat5抑制或小干扰RNA显著影响HepG2和Hep3B细胞中IGF-1诱导的EMT。总之，IGF-1通过Stat5信号通路诱导HCC的EMT。因此，IGF-1/Stat5可作为HCC患者一种潜在的新型治疗策略。