ADAM9 mediates the interleukin-6-induced Epithelial-Mesenchymal transition and metastasis through ROS production in hepatoma cells

作者：Dong, Yinying; Wu, Zhifeng; He, Mingyan; Chen, Yuhan; Chen, Yixing; Shen, Xiaoyun; Zhao, Xiaomei; Zhang, Li; Yuan, Baoying; Zeng, Zhaochong^*

来源：Cancer Letters, 2018, 421: 1-14.

DOI：10.1016/j.canlet.2018.02.010

• Interleukin-6
• A disintegrin and metalloprotease 9
• Epithelial-mesenchymal transition
• ROS
• Hepatocellular carcinoma

Interleukin (IL)-6 has been implicated in the invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular events that mediate this process are poorly understood. Here, we showed that IL-6 promoted the epithelial-mesenchymal transition (EMT) in HCC cell lines, and upregulated a disintegrin and metalloprotease 9 (ADAM9) expression by activating the JNK signaling pathway. ADAM9 was upregulated in human HCCs which promoted HCC cell invasion and the EMT by interacting with NADPH oxidase 1 and inducing reactive oxygen species generation. Knockdown of ADAM9 inhibited the IL-6-induced EMT. Additionally, ADAM9 expression was positively correlated with IL-6 and Snail expression in human HCC specimens. Taken together, our results showed that ADAM9 is an important mediator of IL-6-induced HCC cell migration and invasion, and may provide a novel therapeutic target for HCC management.

• 出版日期2018
• 单位青岛大学; 复旦大学; 南昌大学