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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doaj-b5f035520ae64b008032050e02b14f852020-12-08T01:16:32ZengNature Publishing GroupScientific Reports2045-23222017-08-017111210.1038/s41598-017-08047-1An epithelial-to-mesenchymal transition-inducing potential of granulocyte macrophage colony-stimulating factor in colon cancerYaqiong Chen0Zhi Zhao1Yu Chen2Zhonglin Lv3Xin Ding4Renxi Wang5He Xiao6Chunmei Hou7Beifen Shen8Jiannan Feng9Renfeng Guo10Yan Li11Hui Peng12Gencheng Han13Guojiang Chen14Department of Immunology, Institute of Basic Medical SciencesDepartment of Pathology, Yihe Hospital, Henan UniversityDepartment of Experimental Animals, Zhejiang Academy of Traditional Chinese MedicineDepartment of Immunology, Institute of Basic Medical SciencesGraduate School, Anhui Medical UniversityDepartment of Immunology, Institute of Basic Medical SciencesDepartment of Immunology, Institute of Basic Medical SciencesDepartment of Immunology, Institute of Basic Medical SciencesDepartment of Immunology, Institute of Basic Medical SciencesDepartment of Immunology, Institute of Basic Medical SciencesDepartment of Pathology, University of MichiganDepartment of Immunology, Institute of Basic Medical SciencesCollege of Pharmacy, China Pharmaceutical UniversityDepartment of Immunology, Institute of Basic Medical SciencesDepartment of Immunology, Institute of Basic Medical SciencesAbstract 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.https://doi.org/10.1038/s41598-017-08047-1 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-08047-1 |
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