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03 March 2018 : Laboratory Research

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

Wei Wang12ABCDEF, Feiyu Liu3ABCDEF, Chaoyang Wang2BC, Chengde Wang2CD, Yijun Tang2D, Zhongmin Jiang1AE*

DOI: 10.12659/MSM.906266

Med Sci Monit 2018; 24: LBR1282-1294

Abstract

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.

Keywords: Receptor Activator of Nuclear Factor-kappa B, src-Family Kinases

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750