Src 通过 Fn14 介导的 NF-κB 信号促进人非小细胞肺癌细胞的转移。

Src Promotes Metastasis of Human Non-Small Cell Lung Cancer Cells through Fn14-Mediated NF-κB Signaling.

机构信息

Department of Thoracic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China (mainland).

Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China (mainland).

出版信息

Med Sci Monit. 2018 Mar 3;24:1282-1294. doi: 10.12659/msm.906266.

BACKGROUND Src and Fn14 are implicated in the aggressiveness of non-small cell lung cancer (NSCLC) cells, yet the molecular mechanism is not fully understood. MATERIAL AND METHODS The proliferation, migration, and invasion of HCC827 cells with Src knockdown were examined in vitro. The expression of Fn14 and the activation of NF-κB signaling pathway in Src-silenced HCC827 cells were detected by western blot. The role of Fn14 in Src-regulated cell migration/invasion and activation of NF-κB signaling was investigated by overexpressing Fn14 in Src knockdown NSCLC cells. Furthermore, the pro-metastatic role of Src was validated in a NSCLC metastasis mouse model. RESULTS Knockdown of Src inhibited the proliferation, migration, and invasion of HCC827 cells, which was associated with reduced levels of Fn14, p-IκBα, p-IKKβ, and nuclear NF-κB p65. Overexpression of Fn14 restored the potential of migration and invasion as well as the activation of NF-κB signaling in Src-silenced NSCLC cells. In addition, silencing of Src suppressed lung metastasis of HCC827 cells in mice, and inhibited the expression of Fn14 and nuclear translocation of NF-κB p65 in vivo. CONCLUSIONS The data demonstrated that the Src/Fn14/NF-κB axis plays a critical role in NSCLC metastasis.

背景Src 和 Fn14 与非小细胞肺癌（NSCLC）细胞的侵袭性有关，但分子机制尚不完全清楚。

材料和方法在体外检测 Src 敲低的 HCC827 细胞的增殖、迁移和侵袭。通过 Western blot 检测 Src 沉默 HCC827 细胞中 Fn14 的表达和 NF-κB 信号通路的激活。通过在 Src 下调的 NSCLC 细胞中过表达 Fn14 来研究 Fn14 在 Src 调节的细胞迁移/侵袭和 NF-κB 信号激活中的作用。此外，在 NSCLC 转移小鼠模型中验证了 Src 的促转移作用。

结果 Src 的敲低抑制了 HCC827 细胞的增殖、迁移和侵袭，这与 Fn14、p-IκBα、p-IKKβ 和核 NF-κB p65 水平降低有关。过表达 Fn14 恢复了 Src 沉默 NSCLC 细胞的迁移和侵袭潜能以及 NF-κB 信号的激活。此外，Src 的沉默抑制了 HCC827 细胞在小鼠中的肺转移，并抑制了体内 Fn14 的表达和 NF-κB p65 的核易位。

结论数据表明，Src/Fn14/NF-κB 轴在 NSCLC 转移中起关键作用。