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-...
Guardado en:
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Nature Portfolio
2017
|
Materias: | |
Acceso en línea: | https://doaj.org/article/b5f035520ae64b008032050e02b14f85 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:b5f035520ae64b008032050e02b14f85 |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT yaqiongchen anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT zhizhao anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT yuchen anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT zhonglinlv anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT xinding anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT renxiwang anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT hexiao anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT chunmeihou anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT beifenshen anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT jiannanfeng anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT renfengguo anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT yanli anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT huipeng anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT genchenghan anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT guojiangchen anepithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT yaqiongchen epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT zhizhao epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT yuchen epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT zhonglinlv epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT xinding epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT renxiwang epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT hexiao epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT chunmeihou epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT beifenshen epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT jiannanfeng epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT renfengguo epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT yanli epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT huipeng epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT genchenghan epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer AT guojiangchen epithelialtomesenchymaltransitioninducingpotentialofgranulocytemacrophagecolonystimulatingfactorincoloncancer |
_version_ |
1718394948214063104 |