CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition.
CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition.
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DOI：
10.7150/ijbs.73275
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发表时间：
2022
影响因子：
9.2
通讯作者：
He, Jie
中科院分区：
文献类型：
--
作者：
Fan, Tao;Li, Shuofeng;Xiao, Chu;Tian, He;Zheng, Yujia;Liu, Yu;Li, Chunxiang;He, Jie
C-C基序趋化因子配体20（CCL 20）参与多种致癌过程，但其在肺腺癌（LUAD）中的作用尚不清楚。在此，我们探讨了CCL 20在LUAD进展中的作用机制。我们基于4个独立队列中1544例LUAD病例的完整转录组测序数据进行了生物信息学分析，以评估CCL 20调控的信号通路。我们建立了CCL 20敲低的A549和H358细胞系，以探索CCL 20如何在体外和体内实验中促进肿瘤进展。使用另一个独立队列的348例接受抗PD-L1药物（atezolizumab）治疗的尿路上皮癌患者，我们探索了CCL 20和TGF-β对免疫治疗疗效的协同作用。CCL 20高表达是LUAD患者预后不良的标志物，并与LUAD中增强的上皮-间质转化（EMT）、炎症反应和激活的TNF途径相关。CCL 20基因敲低抑制LUAD细胞的EMT过程和细胞增殖。低CCL 20表达阻断了高TGF-β对生存的不利影响，并有效改善了患者对抗PD-L1治疗的反应。总的来说，我们揭示了基于最大样本量的CCL 20促进LUAD进展的潜在机制。CCL 20和TGF-β对免疫检查点阻断治疗功效的协同抑制作用提供了免疫治疗抗性的新观点。
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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人类抗原R调节的CCL20有助于骨化乳腺癌骨转移。
影响因子：
4.6
作者：
Lee SK;Park KK;Kim HJ;Park J;Son SH;Kim KR;Chung WY
通讯作者：
Chung WY
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影响因子：
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作者：
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通讯作者：
Liu S
DOI：
10.1016/j.jtho.2020.03.003
发表时间：
2020-07
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Paz-Ares L;Kim TM;Vicente D;Felip E;Lee DH;Lee KH;Lin CC;Flor MJ;Di Nicola M;Alvarez RM;Dussault I;Helwig C;Ojalvo LS;Gulley JL;Cho BC
通讯作者：
Cho BC
影响因子：
11.4
作者：
Lee, Jaewang;You, Ji Hyeon;Roh, Jong-Lyel
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Roh, Jong-Lyel
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影响因子：
9.7
作者：
Liu, Wan;Wang, Wenjing;Di, Wen
通讯作者：
Di, Wen