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TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway

Tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan (Trp) metabolism has been linked with some malignant traits of various cancers. Kyn, the main product of Trp metabolism pathway catalyzed by TDO2 and indoleamine 2,3-dioxygenase (IDO) in tumor cells, was also demonstrated to activat...

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Autores principales: Li, Lei, Wang, Tao, Li, Shanbao, Chen, Zhengqian, Wu, Junyi, Cao, Wanyue, Wo, Qi, Qin, Xuebin, Xu, Junming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851084/
https://www.ncbi.nlm.nih.gov/pubmed/33542896
http://dx.doi.org/10.3389/fonc.2020.562823
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author Li, Lei
Wang, Tao
Li, Shanbao
Chen, Zhengqian
Wu, Junyi
Cao, Wanyue
Wo, Qi
Qin, Xuebin
Xu, Junming
author_facet Li, Lei
Wang, Tao
Li, Shanbao
Chen, Zhengqian
Wu, Junyi
Cao, Wanyue
Wo, Qi
Qin, Xuebin
Xu, Junming
author_sort Li, Lei
collection PubMed
description Tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan (Trp) metabolism has been linked with some malignant traits of various cancers. Kyn, the main product of Trp metabolism pathway catalyzed by TDO2 and indoleamine 2,3-dioxygenase (IDO) in tumor cells, was also demonstrated to activate aryl hydrocarbon receptor (AhR), which may regulate cancer growth and invasion in some malignancies. However, whether TDO2 participates in the metastasis and invasion of HCC has not been explored before. The underlying mechanism played by TDO2 in this process still requires further investigation. Here, we demonstrated that overexpression of TDO2 correlates with advanced stage or malignant traits in HCC patients. Knockdown or inhibition of TDO2 suppressed the migration and invasion of HCC cells in vitro and in vivo. Epithelial to mesenchymal transition (EMT) is an essential program happened in the initial phase of cancer metastasis. We found that in HCC cells, TDO2 promoted the EMT process evidenced by altered levels of biomarkers for EMT. Mechanically, TDO2 regulated the Kyn production in HCC cell via activated aryl hydrocarbon receptor (AhR). Together, these results indicate that TDO2 promotes the EMT of hepatocellular carcinoma through activating Kyn-AhR pathway, thereby participating in the metastasis and invasion of HCC.
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spelling pubmed-78510842021-02-03 TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway Li, Lei Wang, Tao Li, Shanbao Chen, Zhengqian Wu, Junyi Cao, Wanyue Wo, Qi Qin, Xuebin Xu, Junming Front Oncol Oncology Tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan (Trp) metabolism has been linked with some malignant traits of various cancers. Kyn, the main product of Trp metabolism pathway catalyzed by TDO2 and indoleamine 2,3-dioxygenase (IDO) in tumor cells, was also demonstrated to activate aryl hydrocarbon receptor (AhR), which may regulate cancer growth and invasion in some malignancies. However, whether TDO2 participates in the metastasis and invasion of HCC has not been explored before. The underlying mechanism played by TDO2 in this process still requires further investigation. Here, we demonstrated that overexpression of TDO2 correlates with advanced stage or malignant traits in HCC patients. Knockdown or inhibition of TDO2 suppressed the migration and invasion of HCC cells in vitro and in vivo. Epithelial to mesenchymal transition (EMT) is an essential program happened in the initial phase of cancer metastasis. We found that in HCC cells, TDO2 promoted the EMT process evidenced by altered levels of biomarkers for EMT. Mechanically, TDO2 regulated the Kyn production in HCC cell via activated aryl hydrocarbon receptor (AhR). Together, these results indicate that TDO2 promotes the EMT of hepatocellular carcinoma through activating Kyn-AhR pathway, thereby participating in the metastasis and invasion of HCC. Frontiers Media S.A. 2021-01-19 /pmc/articles/PMC7851084/ /pubmed/33542896 http://dx.doi.org/10.3389/fonc.2020.562823 Text en Copyright © 2021 Li, Wang, Li, Chen, Wu, Cao, Wo, Qin and Xu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Li, Lei
Wang, Tao
Li, Shanbao
Chen, Zhengqian
Wu, Junyi
Cao, Wanyue
Wo, Qi
Qin, Xuebin
Xu, Junming
TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway
title TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway
title_full TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway
title_fullStr TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway
title_full_unstemmed TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway
title_short TDO2 Promotes the EMT of Hepatocellular Carcinoma Through Kyn-AhR Pathway
title_sort tdo2 promotes the emt of hepatocellular carcinoma through kyn-ahr pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851084/
https://www.ncbi.nlm.nih.gov/pubmed/33542896
http://dx.doi.org/10.3389/fonc.2020.562823
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