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

• DOI: 10.1038/s41598-017-08047-1
• Publication Date: 2017-08-09T15:06:33Z
• Authors: 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
• Keywords: 0303 health sciences; Epithelial-Mesenchymal Transition; Science; Q; R; Granulocyte-Macrophage Colony-Stimulating Factor; Zinc Finger E-box-Binding Homeobox 1; Article; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Cell Movement; Drug Resistance, Neoplasm; Cell Line, Tumor; Colonic Neoplasms; Medicine; Animals; Humans; Mitogen-Activated Protein Kinases; Neoplasm Metastasis; Extracellular Signal-Regulated MAP Kinases; Signal Transduction

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 tumor niches. However, little known about effect GM-CSF on cancer cells. Herein, we show chronic exposure colon cells GM-CSF, harbor its receptor, leads occurrence epithelial mesenchymal transition (EMT), time and dose-dependent manners. These GM-CSF-educated exhibit enhanced ability motility vitro vivo . Furthermore, stimulation renders more resistant cytotoxic agents. Mechanistic investigation reveals MAPK/ERK signaling EMT-inducing transcription ZEB1 are critical mediate these effects GM-CSF. In specimen CRC patients, high-level expression positively correlates with local metastases lymph nodes. Moreover, co-expression receptors as well phosphorylated ERK1/2 observed. Thus, our study for first identifies a by inducing EMT.