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CX3CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer
Authors:Mengtian Fan  Jinghong Wu  Xian Li  Yingjiu Jiang  Xiaowen Wang  Mengjun Bie  Yaguang Weng  Sicheng Chen  Bin Chen  Liqin An  Menghao Zhang  Gaigai Huang  Mengying Zhu  Qiong Shi
Institution:1. Ministry of Education Key Laboratory of Diagnostic Medicine, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China

Contribution: Data curation (equal), Writing - original draft (equal);2. Department of Pathology, The first Affiliated Hospital, Chongqing Medical University, Chongqing, China

Contribution: Resources (supporting);3. Cardiothoracic Surgery of the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Contribution: Resources (supporting);4. Cardiothoracic Surgery of the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Contribution: Methodology (supporting);5. Ministry of Education Key Laboratory of Diagnostic Medicine, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China

Contribution: Formal analysis (supporting);6. Cardiothoracic Surgery of the First Affiliated Hospital, Chongqing Medical University, Chongqing, China

Contribution: Software (supporting);7. Ministry of Education Key Laboratory of Diagnostic Medicine, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China

Contribution: Software (supporting);8. Ministry of Education Key Laboratory of Diagnostic Medicine, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China

Contribution: Writing - original draft (supporting);9. Ministry of Education Key Laboratory of Diagnostic Medicine, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China

Abstract:It has been reported that chemokine CX3CL1 can regulate various tumours by binding to its unique receptor CX3CR1. However, the effect of CX3CL1-CX3CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX3CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX3CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX3CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX3CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX3CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX3CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX3CL1 may be a potential molecule in regulating the migration and invasion of lung cancer.
Keywords:cancer  cortactin  CX3CL1  invasion  lung
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