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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Metastasis | Research

TRAIL promotes epithelial-to-mesenchymal transition by inducing PD-L1 expression in esophageal squamous cell carcinomas

Authors: Huanyu Zhang, Guohui Qin, Chaoqi Zhang, Huiyun Yang, Jinyan Liu, Hongwei Hu, Peng Wu, Shasha Liu, Li Yang, Xinfeng Chen, Xueke Zhao, Lidong Wang, Yi Zhang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL) was initially considered an immunity guard; however, its function remains controversial. Besides immune cells, lung and colon cancer cells have also been reported to express TRAIL, which can promote tumor invasion and metastasis. However, the biological function and underlying mechanism of action of TRAIL in esophageal squamous cell carcinoma (ESCC) remain poorly elucidated.

Methods

The ESCC cells stemness, migration, and proliferation ability was assessed by sphere formation, Transwell, and CCK8 assay. The stemness- and epithelial-mesenchymal transition (EMT)- related genes expression levels were analyzed by Western blot and RT-qPCR. The signal activation was conducted by Western blot. The xenograft mouse experiments and lung metastasis model were performed to confirm our findings in vitro.

Results

Herein, we found that TRAIL is a negative predictor in patients with ESCC. To further investigate the biological function of TRAIL, we established TRAIL knockdown and overexpression ESCC cell lines and found that TRAIL induced EMT and promoted tumor aggressiveness. Furthermore, we demonstrated that TRAIL- overexpressing cells upregulated PD-L1 expression, which was dependent on the p-ERK/STAT3 signaling pathway. We obtained similar results when using recombinant human TRAIL. Finally, we validated the biological role and mechanism of action of TRAIL in vivo.

Conclusions

These findings demonstrate that TRAIL promotes ESCC progression by enhancing PD-L1 expression, which induces EMT. This may explain the failure of TRAIL preclinical trials.

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Title: TRAIL promotes epithelial-to-mesenchymal transition by inducing PD-L1 expression in esophageal squamous cell carcinomas
Authors: Huanyu Zhang
Guohui Qin
Chaoqi Zhang
Huiyun Yang
Jinyan Liu
Hongwei Hu
Peng Wu
Shasha Liu
Li Yang
Xinfeng Chen
Xueke Zhao
Lidong Wang
Yi Zhang
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Metastasis
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-01972-0

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