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The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms

Postoperative recurrence and metastasis have crucial roles in the poor prognosis of gastric cancer patients. Previous studies have indicated that gastric cancer originates from cancer stem cells (CSCs), and some investigators have found that a particular subset of CSCs possesses higher metastatic ca...

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Autores principales: Jiang, Y-X, Yang, S-W, Li, P-A, Luo, X, Li, Z-Y, Hao, Y-X, Yu, P-W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340802/
https://www.ncbi.nlm.nih.gov/pubmed/27524415
http://dx.doi.org/10.1038/onc.2016.291
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author Jiang, Y-X
Yang, S-W
Li, P-A
Luo, X
Li, Z-Y
Hao, Y-X
Yu, P-W
author_facet Jiang, Y-X
Yang, S-W
Li, P-A
Luo, X
Li, Z-Y
Hao, Y-X
Yu, P-W
author_sort Jiang, Y-X
collection PubMed
description Postoperative recurrence and metastasis have crucial roles in the poor prognosis of gastric cancer patients. Previous studies have indicated that gastric cancer originates from cancer stem cells (CSCs), and some investigators have found that a particular subset of CSCs possesses higher metastatic capacity. However, the specific mechanism remains uncertain. In the present study, we aimed to explore the biological functions of the inflammatory cytokine interleukin-17 (IL-17) in gastric cancer metastasis and the distinct IL-17-induced transformation of quiescent gastric CSCs. Our results showed that invasive gastric CSCs were CD26+ and CXCR4+ and were closely associated with increased metastatic ability. The quiescent gastric CSCs, which were CD26− and CXCR4−, were exposed to appropriate concentrations of IL-17; this resulted in the decreased expression of E-cadherin and the increased expression of vimentin and N-cadherin. In addition, the upregulation of IL-17 both in vitro and in vivo resulted in a significant induction of invasion, migration and tumor formation ability in gastric CSCs compared with the control group, which was not treated with IL-17. Further experiments indicated that the activation of the downstream phosphorylated signal transducer and activator of transcription 3 (STAT3) transcription factor pathway was facilitated by IL-17. On the contrary, the downregulation of STAT3 by the specific inhibitor Stattic significantly reversed the IL-17-induced epithelial–mesenchymal transition (EMT)-associated properties of quiescent gastric CSCs. Moreover, tumorigenesis and metastasis were suppressed. Taken together, we suggest that IL-17 is positively correlated with the transformation of quiescent gastric CSCs into invasive gastric CSCs and that targeting IL-17 may emerge as a possible novel therapeutic strategy for gastric cancer.
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spelling pubmed-53408022017-03-21 The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms Jiang, Y-X Yang, S-W Li, P-A Luo, X Li, Z-Y Hao, Y-X Yu, P-W Oncogene Original Article Postoperative recurrence and metastasis have crucial roles in the poor prognosis of gastric cancer patients. Previous studies have indicated that gastric cancer originates from cancer stem cells (CSCs), and some investigators have found that a particular subset of CSCs possesses higher metastatic capacity. However, the specific mechanism remains uncertain. In the present study, we aimed to explore the biological functions of the inflammatory cytokine interleukin-17 (IL-17) in gastric cancer metastasis and the distinct IL-17-induced transformation of quiescent gastric CSCs. Our results showed that invasive gastric CSCs were CD26+ and CXCR4+ and were closely associated with increased metastatic ability. The quiescent gastric CSCs, which were CD26− and CXCR4−, were exposed to appropriate concentrations of IL-17; this resulted in the decreased expression of E-cadherin and the increased expression of vimentin and N-cadherin. In addition, the upregulation of IL-17 both in vitro and in vivo resulted in a significant induction of invasion, migration and tumor formation ability in gastric CSCs compared with the control group, which was not treated with IL-17. Further experiments indicated that the activation of the downstream phosphorylated signal transducer and activator of transcription 3 (STAT3) transcription factor pathway was facilitated by IL-17. On the contrary, the downregulation of STAT3 by the specific inhibitor Stattic significantly reversed the IL-17-induced epithelial–mesenchymal transition (EMT)-associated properties of quiescent gastric CSCs. Moreover, tumorigenesis and metastasis were suppressed. Taken together, we suggest that IL-17 is positively correlated with the transformation of quiescent gastric CSCs into invasive gastric CSCs and that targeting IL-17 may emerge as a possible novel therapeutic strategy for gastric cancer. Nature Publishing Group 2017-03-02 2016-08-15 /pmc/articles/PMC5340802/ /pubmed/27524415 http://dx.doi.org/10.1038/onc.2016.291 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Jiang, Y-X
Yang, S-W
Li, P-A
Luo, X
Li, Z-Y
Hao, Y-X
Yu, P-W
The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms
title The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms
title_full The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms
title_fullStr The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms
title_full_unstemmed The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms
title_short The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms
title_sort promotion of the transformation of quiescent gastric cancer stem cells by il-17 and the underlying mechanisms
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340802/
https://www.ncbi.nlm.nih.gov/pubmed/27524415
http://dx.doi.org/10.1038/onc.2016.291
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