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Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of esophageal cancer (EC). ESCC accounts for 90% of EC. Recurrence after primary treatment is the main reason for poor survival. Therefore, recurrence prevention is a promising strategy for extendin...

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Autores principales: Wu, Xiangyu, Wang, Zitong, Jiang, Yanan, Zhou, Hao, Li, Ang, Wei, Yaxing, Bao, Zhuo, Wang, Donghao, Zhao, Jimin, Chen, Xinhuan, Guo, Yaping, Dong, Zigang, Liu, Kangdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372369/
https://www.ncbi.nlm.nih.gov/pubmed/34422635
http://dx.doi.org/10.3389/fonc.2021.683241
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author Wu, Xiangyu
Wang, Zitong
Jiang, Yanan
Zhou, Hao
Li, Ang
Wei, Yaxing
Bao, Zhuo
Wang, Donghao
Zhao, Jimin
Chen, Xinhuan
Guo, Yaping
Dong, Zigang
Liu, Kangdong
author_facet Wu, Xiangyu
Wang, Zitong
Jiang, Yanan
Zhou, Hao
Li, Ang
Wei, Yaxing
Bao, Zhuo
Wang, Donghao
Zhao, Jimin
Chen, Xinhuan
Guo, Yaping
Dong, Zigang
Liu, Kangdong
author_sort Wu, Xiangyu
collection PubMed
description Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of esophageal cancer (EC). ESCC accounts for 90% of EC. Recurrence after primary treatment is the main reason for poor survival. Therefore, recurrence prevention is a promising strategy for extending the 5-year survival rate. Here, we found tegaserod maleate could inhibit ESCC proliferation both in vivo and in vitro. Proteomics analysis revealed that tegaserod maleate suppressed the peroxisome signaling pathway, in which the key molecules peroxisome membrane protein 11B (PEX11B) and peroxisome membrane protein 13 (PEX13) were downregulated. The immunofluorescence, catalase activity assay, and reactive oxygen species (ROS) confirmed that downregulation of these proteins was related to impaired peroxisome function. Furthermore, we found that PEX11B and PEX13 were highly expressed in ESCC, and knockout of PEX11B and PEX13 further demonstrated the antitumor effect of tegaserod maleate. Importantly, tegaserod maleate repressed ESCC tumor growth in a patient-derived xenograft (PDX) model in vivo. Our findings conclusively demonstrated that tegaserod maleate inhibits the proliferation of ESCC by suppressing the peroxisome pathway.
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spelling pubmed-83723692021-08-19 Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway Wu, Xiangyu Wang, Zitong Jiang, Yanan Zhou, Hao Li, Ang Wei, Yaxing Bao, Zhuo Wang, Donghao Zhao, Jimin Chen, Xinhuan Guo, Yaping Dong, Zigang Liu, Kangdong Front Oncol Oncology Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of esophageal cancer (EC). ESCC accounts for 90% of EC. Recurrence after primary treatment is the main reason for poor survival. Therefore, recurrence prevention is a promising strategy for extending the 5-year survival rate. Here, we found tegaserod maleate could inhibit ESCC proliferation both in vivo and in vitro. Proteomics analysis revealed that tegaserod maleate suppressed the peroxisome signaling pathway, in which the key molecules peroxisome membrane protein 11B (PEX11B) and peroxisome membrane protein 13 (PEX13) were downregulated. The immunofluorescence, catalase activity assay, and reactive oxygen species (ROS) confirmed that downregulation of these proteins was related to impaired peroxisome function. Furthermore, we found that PEX11B and PEX13 were highly expressed in ESCC, and knockout of PEX11B and PEX13 further demonstrated the antitumor effect of tegaserod maleate. Importantly, tegaserod maleate repressed ESCC tumor growth in a patient-derived xenograft (PDX) model in vivo. Our findings conclusively demonstrated that tegaserod maleate inhibits the proliferation of ESCC by suppressing the peroxisome pathway. Frontiers Media S.A. 2021-08-04 /pmc/articles/PMC8372369/ /pubmed/34422635 http://dx.doi.org/10.3389/fonc.2021.683241 Text en Copyright © 2021 Wu, Wang, Jiang, Zhou, Li, Wei, Bao, Wang, Zhao, Chen, Guo, Dong and Liu https://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
Wu, Xiangyu
Wang, Zitong
Jiang, Yanan
Zhou, Hao
Li, Ang
Wei, Yaxing
Bao, Zhuo
Wang, Donghao
Zhao, Jimin
Chen, Xinhuan
Guo, Yaping
Dong, Zigang
Liu, Kangdong
Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway
title Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway
title_full Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway
title_fullStr Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway
title_full_unstemmed Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway
title_short Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway
title_sort tegaserod maleate inhibits esophageal squamous cell carcinoma proliferation by suppressing the peroxisome pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372369/
https://www.ncbi.nlm.nih.gov/pubmed/34422635
http://dx.doi.org/10.3389/fonc.2021.683241
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