An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer

Abstract Growing evidence shows that granulocyte macrophage colony-stimulating factor (GM-CSF) has progression-promoting potentials in certain solid tumors, which is largely attributed to the immunomodulatory function of this cytokine in tumor niches. However, little is known about the effect of GM-...

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Autores principales: Yaqiong Chen, Zhi Zhao, Yu Chen, Zhonglin Lv, Xin Ding, Renxi Wang, He Xiao, Chunmei Hou, Beifen Shen, Jiannan Feng, Renfeng Guo, Yan Li, Hui Peng, Gencheng Han, Guojiang Chen
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:b5f035520ae64b008032050e02b14f852021-12-02T11:52:56ZAn epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer10.1038/s41598-017-08047-12045-2322https://doaj.org/article/b5f035520ae64b008032050e02b14f852017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08047-1https://doaj.org/toc/2045-2322Abstract Growing evidence shows that granulocyte macrophage colony-stimulating factor (GM-CSF) has progression-promoting potentials in certain solid tumors, which is largely attributed to the immunomodulatory function of this cytokine in tumor niches. However, little is known about the effect of GM-CSF on cancer cells. Herein, we show that chronic exposure of colon cancer cells to GM-CSF, which harbor its receptor, leads to occurrence of epithelial to mesenchymal transition (EMT), in time and dose-dependent manners. These GM-CSF-educated cancer cells exhibit enhanced ability of motility in vitro and in vivo. Furthermore, GM-CSF stimulation renders colon cancer cells more resistant to cytotoxic agents. Mechanistic investigation reveals that MAPK/ERK signaling and EMT-inducing transcription factor ZEB1 are critical to mediate these effects of GM-CSF. In specimen of CRC patients, high-level expression of GM-CSF positively correlates with local metastases in lymph nodes. Moreover, the co-expression of GM-CSF and its receptors as well as phosphorylated ERK1/2 are observed. Thus, our study for the first time identifies a progression-promoting function of GM-CSF in colon cancer by inducing EMT.Yaqiong ChenZhi ZhaoYu ChenZhonglin LvXin DingRenxi WangHe XiaoChunmei HouBeifen ShenJiannan FengRenfeng GuoYan LiHui PengGencheng HanGuojiang ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yaqiong Chen
Zhi Zhao
Yu Chen
Zhonglin Lv
Xin Ding
Renxi Wang
He Xiao
Chunmei Hou
Beifen Shen
Jiannan Feng
Renfeng Guo
Yan Li
Hui Peng
Gencheng Han
Guojiang Chen
An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer
description Abstract Growing evidence shows that granulocyte macrophage colony-stimulating factor (GM-CSF) has progression-promoting potentials in certain solid tumors, which is largely attributed to the immunomodulatory function of this cytokine in tumor niches. However, little is known about the effect of GM-CSF on cancer cells. Herein, we show that chronic exposure of colon cancer cells to GM-CSF, which harbor its receptor, leads to occurrence of epithelial to mesenchymal transition (EMT), in time and dose-dependent manners. These GM-CSF-educated cancer cells exhibit enhanced ability of motility in vitro and in vivo. Furthermore, GM-CSF stimulation renders colon cancer cells more resistant to cytotoxic agents. Mechanistic investigation reveals that MAPK/ERK signaling and EMT-inducing transcription factor ZEB1 are critical to mediate these effects of GM-CSF. In specimen of CRC patients, high-level expression of GM-CSF positively correlates with local metastases in lymph nodes. Moreover, the co-expression of GM-CSF and its receptors as well as phosphorylated ERK1/2 are observed. Thus, our study for the first time identifies a progression-promoting function of GM-CSF in colon cancer by inducing EMT.
format article
author Yaqiong Chen
Zhi Zhao
Yu Chen
Zhonglin Lv
Xin Ding
Renxi Wang
He Xiao
Chunmei Hou
Beifen Shen
Jiannan Feng
Renfeng Guo
Yan Li
Hui Peng
Gencheng Han
Guojiang Chen
author_facet Yaqiong Chen
Zhi Zhao
Yu Chen
Zhonglin Lv
Xin Ding
Renxi Wang
He Xiao
Chunmei Hou
Beifen Shen
Jiannan Feng
Renfeng Guo
Yan Li
Hui Peng
Gencheng Han
Guojiang Chen
author_sort Yaqiong Chen
title An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer
title_short An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer
title_full An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer
title_fullStr An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer
title_full_unstemmed An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer
title_sort epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancer
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/b5f035520ae64b008032050e02b14f85
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