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BMC Cancer
Published in: BMC Cancer 1/2020

01-12-2020 | Oral Cancer | Research article

CCL18-NIR1 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signaling pathway

Authors: Xiao Jiang, Zhijie Huang, Xiang Sun, Xianghuai Zheng, Jingpeng Liu, Jun Shen, Bo Jia, Haiyun Luo, Zhaoyi Mai, Guodong Chen, Jianjiang Zhao

Published in: BMC Cancer | Issue 1/2020

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Abstract

Background

Chemokine (C-C motif) ligand 18 (CCL18) affects the malignant progression of varying cancers by activating chemokine receptors. Our previous work has shown that CCL18 promotes hyperplasia and invasiveness of oral cancer cells; however, the cognate receptors of CCL18 involved in the pathogenesis of oral squamous cell carcinoma (OSCC) have not yet been identified. This study aimed to investigate the molecular mechanisms which underlie promotive effects of CCL18 on OSCC progression by binding to functional receptors.

Methods

The expression of CCL18 receptor-NIR1 in OSCC was determined by conducting western blot, immunofluorescence, and immunocytochemistry assays. Chi square test was applied to analyze the relationship between expression levels of NIR1 and clinicopathological variables. Recombinant CCL18 (rCCL18), receptor siRNA and JAK specific inhibitor (AG490) were used in experiments investigating the effects of the CCL18-NIR1 axis on growth of cancer cells (i.e., proliferation, and metastasis), epithelial-mesenchymal transition (EMT) and the activation of the JAK2/STAT3 signaling pathway.

Results

NIR1 as functional receptor of CCL18 in OSCC, was found to be significantly upregulated in OSCC and positively related to the TNM stage of OSCC patients. rCCL18 induced the phenotypical alterations in oral cancer cells including cell growth, metastasis and EMT. The JAK2/STAT3 signaling pathway was confirmed to be a downstream pathway mediating the effects of CCL18 in OSCC. AG490 and knockdown of NIR1 could block the effects of rCCL18-induced OSCC.

Conclusion

CCL18 can promote the progression of OSCC by binding NIR1, and the CCL18-NIR1 axis can activate JAK2/STAT3 signaling pathway. The identification of the mechanisms underlying CCL18-mediated promotion of OSCC progression could highlight potential therapeutic targets for treating oral cancer.
Appendix
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Metadata
Title
CCL18-NIR1 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signaling pathway
Authors
Xiao Jiang
Zhijie Huang
Xiang Sun
Xianghuai Zheng
Jingpeng Liu
Jun Shen
Bo Jia
Haiyun Luo
Zhaoyi Mai
Guodong Chen
Jianjiang Zhao
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2020
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-020-07073-z

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