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CX3CL1 通过Src/黏着斑激酶信号通路促进肺癌细胞迁移和侵袭。

CX3CL1 promotes lung cancer cell migration and invasion via the Src/focal adhesion kinase signaling pathway.

机构信息

Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

出版信息

Oncol Rep. 2019 Mar;41(3):1911-1917. doi: 10.3892/or.2019.6957. Epub 2019 Jan 9.

DOI:10.3892/or.2019.6957
PMID:30628679
Abstract

The present study investigated the role of C‑X3‑C motif chemokine ligand 1 (CX3CL1) in lung cancer cell migration and invasion and its potential mechanism. The expression levels of C‑X3‑C motif chemokine receptor 1 (CX3CR1) in six human lung cancer cell lines and one human bronchial epithelial cell line were assessed using reverse transcription‑quantitative polymerase chain reaction and western blotting. Cell proliferation was assessed using the Cell Counting Kit‑8 assay. Cell migration and invasion were examined using the Transwell assay, with and without Matrigel, respectively. The signaling pathway activated by CX3CL1 was analyzed via western blotting and inhibitory migration and invasion assays. CX3CR1 was expressed in the six lung cancer cell lines and one normal lung cell line. The lung cancer cell line, H460, was selected for further study. CX3CL1 did not significantly affect H460 proliferation; however, CX3CL1 did significantly enhance the migration and invasion of H460 cells. The Src/focal adhesion kinase (FAK) signaling pathway was activated in a time‑dependent manner upon stimulation of CX3CL1. However, blocking Src activity with saracatinib prevented CX3CL1‑mediated cell migration and invasion. Therefore, the findings indicated that CX3CL1 promotes lung cancer cell migration and invasion in vitro, and the Src/FAK signaling pathway serves a vital role in this process.

摘要

本研究探讨了 C‑X3‑C 基序趋化因子配体 1(CX3CL1)在肺癌细胞迁移和侵袭中的作用及其潜在机制。采用反转录‑定量聚合酶链反应和 Western blot 检测六种人肺癌细胞系和一种人支气管上皮细胞系中 C‑X3‑C 基序趋化因子受体 1(CX3CR1)的表达水平。使用细胞计数试剂盒‑8 检测细胞增殖。通过 Transwell 实验(分别有无 Matrigel)检测细胞迁移和侵袭。通过 Western blot 和抑制迁移和侵袭实验分析 CX3CL1 激活的信号通路。CX3CR1 在六种肺癌细胞系和一种正常肺细胞系中表达。选择肺癌细胞系 H460 进行进一步研究。CX3CL1 对 H460 增殖没有显著影响,但显著增强了 H460 细胞的迁移和侵袭。CX3CL1 刺激后 Src/黏着斑激酶(FAK)信号通路呈时间依赖性激活。然而,用 saracatinib 阻断Src 活性可防止 CX3CL1 介导的细胞迁移和侵袭。因此,这些发现表明 CX3CL1 促进肺癌细胞在体外的迁移和侵袭,而 Src/FAK 信号通路在此过程中起着至关重要的作用。

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