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The CXCL5/CXCR2 axis contributes to the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells by activating ERK/GSK-3?/snail signalling.


ABSTRACT: BACKGROUND:Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. METHODS:Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3?/Snail signalling pathway. RESULTS:CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3?/Snail signalling pathway. CONCLUSION:The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3?/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC.

SUBMITTER: Qiu WZ 

PROVIDER: S-EPMC5905166 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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The CXCL5/CXCR2 axis contributes to the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells by activating ERK/GSK-3β/snail signalling.

Qiu Wen-Ze WZ   Zhang Hai-Bo HB   Xia Wei-Xiong WX   Ke Liang-Ru LR   Yang Jing J   Yu Ya-Hui YH   Liang Hu H   Huang Xin-Jun XJ   Liu Guo-Ying GY   Li Wang-Zhong WZ   Xiang Yan-Qun YQ   Kang Tie-Bang TB   Guo Xiang X   Lv Xing X  

Journal of experimental & clinical cancer research : CR 20180417 1


<h4>Background</h4>Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear.<h4>Methods</h4>Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXC  ...[more]

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