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Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers...

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Autores principales: Zhao, Yumiao, Sun, Jiaxin, Li, Yin, Zhou, Xiuman, Zhai, Wenjie, Wu, Yahong, Chen, Guanyu, Gou, Shanshan, Sui, Xinghua, Zhao, Wenshan, Qiu, Lu, Yao, Yongjie, Sun, Yixuan, Chen, Chunxia, Qi, Yuanming, Gao, Yanfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463272/
https://www.ncbi.nlm.nih.gov/pubmed/34589400
http://dx.doi.org/10.1016/j.apsb.2021.03.009
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author Zhao, Yumiao
Sun, Jiaxin
Li, Yin
Zhou, Xiuman
Zhai, Wenjie
Wu, Yahong
Chen, Guanyu
Gou, Shanshan
Sui, Xinghua
Zhao, Wenshan
Qiu, Lu
Yao, Yongjie
Sun, Yixuan
Chen, Chunxia
Qi, Yuanming
Gao, Yanfeng
author_facet Zhao, Yumiao
Sun, Jiaxin
Li, Yin
Zhou, Xiuman
Zhai, Wenjie
Wu, Yahong
Chen, Guanyu
Gou, Shanshan
Sui, Xinghua
Zhao, Wenshan
Qiu, Lu
Yao, Yongjie
Sun, Yixuan
Chen, Chunxia
Qi, Yuanming
Gao, Yanfeng
author_sort Zhao, Yumiao
collection PubMed
description Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3β, and polarization of M2 macrophages by upregulating interleukin-8 (IL-8) to accelerate tumor progression in the tumor microenvironment (TME). Collectively, our results discovered that TDO2 could upregulate IL-8 through AKT/GSK3β to direct the polarization of M2 macrophages in ESCC, and suggested that TDO2 could represent as an attractive therapeutic target and prognostic marker to ESCC.
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spelling pubmed-84632722021-09-28 Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway Zhao, Yumiao Sun, Jiaxin Li, Yin Zhou, Xiuman Zhai, Wenjie Wu, Yahong Chen, Guanyu Gou, Shanshan Sui, Xinghua Zhao, Wenshan Qiu, Lu Yao, Yongjie Sun, Yixuan Chen, Chunxia Qi, Yuanming Gao, Yanfeng Acta Pharm Sin B Original Article Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3β, and polarization of M2 macrophages by upregulating interleukin-8 (IL-8) to accelerate tumor progression in the tumor microenvironment (TME). Collectively, our results discovered that TDO2 could upregulate IL-8 through AKT/GSK3β to direct the polarization of M2 macrophages in ESCC, and suggested that TDO2 could represent as an attractive therapeutic target and prognostic marker to ESCC. Elsevier 2021-09 2021-03-09 /pmc/articles/PMC8463272/ /pubmed/34589400 http://dx.doi.org/10.1016/j.apsb.2021.03.009 Text en © 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Zhao, Yumiao
Sun, Jiaxin
Li, Yin
Zhou, Xiuman
Zhai, Wenjie
Wu, Yahong
Chen, Guanyu
Gou, Shanshan
Sui, Xinghua
Zhao, Wenshan
Qiu, Lu
Yao, Yongjie
Sun, Yixuan
Chen, Chunxia
Qi, Yuanming
Gao, Yanfeng
Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway
title Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway
title_full Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway
title_fullStr Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway
title_full_unstemmed Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway
title_short Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway
title_sort tryptophan 2,3-dioxygenase 2 controls m2 macrophages polarization to promote esophageal squamous cell carcinoma progression via akt/gsk3β/il-8 signaling pathway
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463272/
https://www.ncbi.nlm.nih.gov/pubmed/34589400
http://dx.doi.org/10.1016/j.apsb.2021.03.009
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