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Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation

Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, w...

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Autores principales: Zhong, Zhaoming, Hu, Zedong, Jiang, Yue, Sun, Ruimei, Chen, Xue, Chu, Hongying, Zeng, Musheng, Sun, Chuanzheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312338/
https://www.ncbi.nlm.nih.gov/pubmed/27487122
http://dx.doi.org/10.18632/oncotarget.10831
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author Zhong, Zhaoming
Hu, Zedong
Jiang, Yue
Sun, Ruimei
Chen, Xue
Chu, Hongying
Zeng, Musheng
Sun, Chuanzheng
author_facet Zhong, Zhaoming
Hu, Zedong
Jiang, Yue
Sun, Ruimei
Chen, Xue
Chu, Hongying
Zeng, Musheng
Sun, Chuanzheng
author_sort Zhong, Zhaoming
collection PubMed
description Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, we found that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1α activation. Furthermore, the resultant increase in IL-11 expression significantly induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by Akt/GSK3β pathway activation and increased invasive and migratory abilities. Conversely, HIF-1α or IL-11 knockdown, or treating cells with a neutralizing antibody against IL-11, a PI3K inhibitor, or Akt inhibitor V, significantly suppressed the induction of EMT and counteracted the enhancements in invasive and migratory abilities. These results indicate that hypoxia increases IL-11 secretion in ATC cells via HIF-1α induction and that IL-11 then induces EMT in these cells via the PI3K/Akt/GSK3β pathway, ultimately improving their invasive and migratory potential. This study elucidates the prometastatic role played by IL-11 in ATC metastasis and indicates it as a potential target for the treatment of cancer metastasis. However, many questions remain to be explored.
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spelling pubmed-53123382017-03-06 Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation Zhong, Zhaoming Hu, Zedong Jiang, Yue Sun, Ruimei Chen, Xue Chu, Hongying Zeng, Musheng Sun, Chuanzheng Oncotarget Research Paper Metastasis is the major cause of treatment failure in anaplastic thyroid carcinoma (ATC) patients. In the preliminary study, we demonstrated that interleukin (IL)-11 expression is positively correlated with distant metastasis in ATC. However, the mechanisms underlying remain largely unknown. Here, we found that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1α activation. Furthermore, the resultant increase in IL-11 expression significantly induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by Akt/GSK3β pathway activation and increased invasive and migratory abilities. Conversely, HIF-1α or IL-11 knockdown, or treating cells with a neutralizing antibody against IL-11, a PI3K inhibitor, or Akt inhibitor V, significantly suppressed the induction of EMT and counteracted the enhancements in invasive and migratory abilities. These results indicate that hypoxia increases IL-11 secretion in ATC cells via HIF-1α induction and that IL-11 then induces EMT in these cells via the PI3K/Akt/GSK3β pathway, ultimately improving their invasive and migratory potential. This study elucidates the prometastatic role played by IL-11 in ATC metastasis and indicates it as a potential target for the treatment of cancer metastasis. However, many questions remain to be explored. Impact Journals LLC 2016-07-25 /pmc/articles/PMC5312338/ /pubmed/27487122 http://dx.doi.org/10.18632/oncotarget.10831 Text en Copyright: © 2016 Zhong et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhong, Zhaoming
Hu, Zedong
Jiang, Yue
Sun, Ruimei
Chen, Xue
Chu, Hongying
Zeng, Musheng
Sun, Chuanzheng
Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation
title Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation
title_full Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation
title_fullStr Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation
title_full_unstemmed Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation
title_short Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through PI3K/Akt/GSK3β signaling pathway activation
title_sort interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid carcinoma cells through pi3k/akt/gsk3β signaling pathway activation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312338/
https://www.ncbi.nlm.nih.gov/pubmed/27487122
http://dx.doi.org/10.18632/oncotarget.10831
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