Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China; Department of Radiation Oncology, The Affiliated Hospital Qingdao University, 16 Jiangsu Road, Qingdao 266003, Shandong, China.
Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
Cancer Lett. 2018 May 1;421:1-14. doi: 10.1016/j.canlet.2018.02.010. Epub 2018 Feb 10.
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.
白细胞介素 (IL)-6 被认为与肝细胞癌 (HCC) 的侵袭和转移有关。然而，介导这一过程的分子事件尚不清楚。在这里，我们表明 IL-6 通过激活 JNK 信号通路促进 HCC 细胞系中的上皮-间充质转化 (EMT)，并上调 a disintegrin and metalloprotease 9 (ADAM9) 的表达。ADAM9 在人 HCC 中上调，通过与 NADPH 氧化酶 1 相互作用并诱导活性氧生成，促进 HCC 细胞侵袭和 EMT。ADAM9 的敲低抑制了 IL-6 诱导的 EMT。此外，ADAM9 的表达与人 HCC 标本中的 IL-6 和 Snail 表达呈正相关。总之，我们的研究结果表明 ADAM9 是 IL-6 诱导的 HCC 细胞迁移和侵袭的重要介质，可能为 HCC 的治疗提供新的靶点。
