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IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells

Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide due to the distant metastases. Compelling evidence has reported that epithelial-mesenchymal transition (EMT) is involved in promoting cancer invasion and metastasis. However, the precise molecular events that...

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Autores principales: Cao, Hui, Zhang, Jing, Liu, Hong, Wan, Ledong, Zhang, Honghe, Huang, Qiong, Xu, Enping, Lai, Maode
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308644/
https://www.ncbi.nlm.nih.gov/pubmed/27533463
http://dx.doi.org/10.18632/oncotarget.11282
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author Cao, Hui
Zhang, Jing
Liu, Hong
Wan, Ledong
Zhang, Honghe
Huang, Qiong
Xu, Enping
Lai, Maode
author_facet Cao, Hui
Zhang, Jing
Liu, Hong
Wan, Ledong
Zhang, Honghe
Huang, Qiong
Xu, Enping
Lai, Maode
author_sort Cao, Hui
collection PubMed
description Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide due to the distant metastases. Compelling evidence has reported that epithelial-mesenchymal transition (EMT) is involved in promoting cancer invasion and metastasis. However, the precise molecular events that initiate this complex EMT process remain poorly understood. Here, we showed that the pleiotropic cytokine interleukin-13 (IL-13) could induce an aggressive phenotype displaying EMT by enhancing the expression of EMT-promoting factor ZEB1. Importantly, STAT6 signaling inhibitor and STAT6 knockdown significantly reversed IL-13-induced EMT and ZEB1 induction in CRC cells, whereas ectopic STAT6 expression in STAT6(null) CRC cell line markedly promoted EMT in the present of IL-13. ChIP-PCR and Luciferase assays revealed that activated STAT6 directly bound to the promoter of ZEB1. Otherwise, we found IL-13 also up-regulated the stem cell markers (nanog, CD44, CD133 and CD166) and promoted cell migration and invasion through STAT6 pathway. We also found that siRNA-mediated knockdown of IL-13Rα1 could reverse IL-13-induced ZEB1 and EMT changes by preventing STAT6 signaling. Finally, we demonstrated positive correlation between IL-13Rα1 and ZEB1 at mRNA levels in human CRC samples. Taken together, our findings first demonstrated that IL-13/IL-13Rα1/STAT6/ZEB1 pathway plays a critical role in promoting EMT and aggressiveness of CRC.
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spelling pubmed-53086442017-03-09 IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells Cao, Hui Zhang, Jing Liu, Hong Wan, Ledong Zhang, Honghe Huang, Qiong Xu, Enping Lai, Maode Oncotarget Research Paper Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide due to the distant metastases. Compelling evidence has reported that epithelial-mesenchymal transition (EMT) is involved in promoting cancer invasion and metastasis. However, the precise molecular events that initiate this complex EMT process remain poorly understood. Here, we showed that the pleiotropic cytokine interleukin-13 (IL-13) could induce an aggressive phenotype displaying EMT by enhancing the expression of EMT-promoting factor ZEB1. Importantly, STAT6 signaling inhibitor and STAT6 knockdown significantly reversed IL-13-induced EMT and ZEB1 induction in CRC cells, whereas ectopic STAT6 expression in STAT6(null) CRC cell line markedly promoted EMT in the present of IL-13. ChIP-PCR and Luciferase assays revealed that activated STAT6 directly bound to the promoter of ZEB1. Otherwise, we found IL-13 also up-regulated the stem cell markers (nanog, CD44, CD133 and CD166) and promoted cell migration and invasion through STAT6 pathway. We also found that siRNA-mediated knockdown of IL-13Rα1 could reverse IL-13-induced ZEB1 and EMT changes by preventing STAT6 signaling. Finally, we demonstrated positive correlation between IL-13Rα1 and ZEB1 at mRNA levels in human CRC samples. Taken together, our findings first demonstrated that IL-13/IL-13Rα1/STAT6/ZEB1 pathway plays a critical role in promoting EMT and aggressiveness of CRC. Impact Journals LLC 2016-08-13 /pmc/articles/PMC5308644/ /pubmed/27533463 http://dx.doi.org/10.18632/oncotarget.11282 Text en Copyright: © 2016 Cao 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
Cao, Hui
Zhang, Jing
Liu, Hong
Wan, Ledong
Zhang, Honghe
Huang, Qiong
Xu, Enping
Lai, Maode
IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells
title IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells
title_full IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells
title_fullStr IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells
title_full_unstemmed IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells
title_short IL-13/STAT6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells
title_sort il-13/stat6 signaling plays a critical role in the epithelial-mesenchymal transition of colorectal cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308644/
https://www.ncbi.nlm.nih.gov/pubmed/27533463
http://dx.doi.org/10.18632/oncotarget.11282
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