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CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2022 Jun 27; Vol. 18 (11), pp. 4275-4288. Date of Electronic Publication: 2022 Jun 27 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- 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.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Cell Line, Tumor
Cell Movement
Cell Proliferation
Chemokine CCL20 genetics
Chemokine CCL20 metabolism
Chemokine CCL20 pharmacology
Chemokines metabolism
Epithelial-Mesenchymal Transition genetics
Gene Expression Regulation, Neoplastic
Humans
Ligands
Transforming Growth Factor beta metabolism
Adenocarcinoma genetics
Adenocarcinoma of Lung drug therapy
Adenocarcinoma of Lung genetics
Carcinoma, Transitional Cell
Lung Neoplasms drug therapy
Lung Neoplasms genetics
Lung Neoplasms metabolism
Urinary Bladder Neoplasms
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 18
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35864953
- Full Text :
- https://doi.org/10.7150/ijbs.73275