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CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition

C-C motif chemokine ligand 20 (CCL20) participates in multiple oncogenic processes, but its role in lung adenocarcinoma (LUAD) is unclear. Herein, we explored the mechanism by which CCL20 works in LUAD progression. We performed bioinformatical analyses based on the complete transcriptome sequencing...

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Autores principales: Fan, Tao, Li, Shuofeng, Xiao, Chu, Tian, He, Zheng, Yujia, Liu, Yu, Li, Chunxiang, He, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295072/
https://www.ncbi.nlm.nih.gov/pubmed/35864953
http://dx.doi.org/10.7150/ijbs.73275
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author Fan, Tao
Li, Shuofeng
Xiao, Chu
Tian, He
Zheng, Yujia
Liu, Yu
Li, Chunxiang
He, Jie
author_facet Fan, Tao
Li, Shuofeng
Xiao, Chu
Tian, He
Zheng, Yujia
Liu, Yu
Li, Chunxiang
He, Jie
author_sort Fan, Tao
collection PubMed
description C-C motif chemokine ligand 20 (CCL20) participates in multiple oncogenic processes, but its role in lung adenocarcinoma (LUAD) is unclear. Herein, we explored the mechanism by which CCL20 works in LUAD progression. We performed bioinformatical analyses based on the complete transcriptome sequencing data from 1544 LUAD cases in 4 independent cohorts to evaluate signaling pathways regulated by CCL20. We established A549 and H358 cell lines with CCL20 knockdown to explore how CCL20 promotes tumor progression in vitro and in vivo experiments. Using another independent cohort of 348 urothelial carcinoma patients treated with the anti-PD-L1 agent (atezolizumab), we explored the synergistic effect of CCL20 and TGF-β on immunotherapy efficacy. High CCL20 expression is a poor prognostic marker for LUAD patients, and is associated with enhanced epithelial-mesenchymal transition (EMT), inflammatory response, and activated TNF pathway in LUAD. CCL20 knockdown restrained the EMT process and cell proliferation of LUAD cells in vitro and in vivo. Low CCL20 expression blocked the detrimental effects of high TGF-β on survival and effectively improved patients' response to anti-PD-L1 therapy. Collectively, we revealed the underlying mechanisms by which CCL20 promotes LUAD progression based on the largest sample size. The synergistic inhibitory effect of CCL20 and TGF-β on immune-checkpoint blockade therapy efficacy provides new views of immunotherapy resistance.
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spelling pubmed-92950722022-07-20 CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition Fan, Tao Li, Shuofeng Xiao, Chu Tian, He Zheng, Yujia Liu, Yu Li, Chunxiang He, Jie Int J Biol Sci Research Paper C-C motif chemokine ligand 20 (CCL20) participates in multiple oncogenic processes, but its role in lung adenocarcinoma (LUAD) is unclear. Herein, we explored the mechanism by which CCL20 works in LUAD progression. We performed bioinformatical analyses based on the complete transcriptome sequencing data from 1544 LUAD cases in 4 independent cohorts to evaluate signaling pathways regulated by CCL20. We established A549 and H358 cell lines with CCL20 knockdown to explore how CCL20 promotes tumor progression in vitro and in vivo experiments. Using another independent cohort of 348 urothelial carcinoma patients treated with the anti-PD-L1 agent (atezolizumab), we explored the synergistic effect of CCL20 and TGF-β on immunotherapy efficacy. High CCL20 expression is a poor prognostic marker for LUAD patients, and is associated with enhanced epithelial-mesenchymal transition (EMT), inflammatory response, and activated TNF pathway in LUAD. CCL20 knockdown restrained the EMT process and cell proliferation of LUAD cells in vitro and in vivo. Low CCL20 expression blocked the detrimental effects of high TGF-β on survival and effectively improved patients' response to anti-PD-L1 therapy. Collectively, we revealed the underlying mechanisms by which CCL20 promotes LUAD progression based on the largest sample size. The synergistic inhibitory effect of CCL20 and TGF-β on immune-checkpoint blockade therapy efficacy provides new views of immunotherapy resistance. Ivyspring International Publisher 2022-06-27 /pmc/articles/PMC9295072/ /pubmed/35864953 http://dx.doi.org/10.7150/ijbs.73275 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Fan, Tao
Li, Shuofeng
Xiao, Chu
Tian, He
Zheng, Yujia
Liu, Yu
Li, Chunxiang
He, Jie
CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition
title CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition
title_full CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition
title_fullStr CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition
title_full_unstemmed CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition
title_short CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition
title_sort ccl20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295072/
https://www.ncbi.nlm.nih.gov/pubmed/35864953
http://dx.doi.org/10.7150/ijbs.73275
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