The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells

The C-X-C motif chemokine receptor 4 (CXCR4) pathway can promote tumor metastasis but is dependent on cross talk with other signaling pathways. The MET proto-oncogene (c-MET) participates in metastasis and is highly expressed in gastric cancer. However, the relationship between CXCR4 and c-MET signa...

Full description

Bibliographic Details
Main Authors:	Yu Cheng, Yongxi Song, Jinglei Qu, Xiaofang Che, Na Song, Yibo Fan, Ti Wen, Ling Xu, Jing Gong, Xiaoxun Wang, Chenlu Zhang, Xiujuan Qu, Yunpeng Liu
Format:	Article
Language:	English
Published:	Elsevier 2018-04-01
Series:	Translational Oncology
Online Access:	http://www.sciencedirect.com/science/article/pii/S1936523317304199

id	doaj-e3ce16d875dc4466b48e59db0e92951a
record_format	Article
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Yu Cheng Yongxi Song Jinglei Qu Xiaofang Che Na Song Yibo Fan Ti Wen Ling Xu Jing Gong Xiaoxun Wang Chenlu Zhang Xiujuan Qu Yunpeng Liu
spellingShingle	Yu Cheng Yongxi Song Jinglei Qu Xiaofang Che Na Song Yibo Fan Ti Wen Ling Xu Jing Gong Xiaoxun Wang Chenlu Zhang Xiujuan Qu Yunpeng Liu The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells Translational Oncology
author_facet	Yu Cheng Yongxi Song Jinglei Qu Xiaofang Che Na Song Yibo Fan Ti Wen Ling Xu Jing Gong Xiaoxun Wang Chenlu Zhang Xiujuan Qu Yunpeng Liu
author_sort	Yu Cheng
title	The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells
title_short	The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells
title_full	The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells
title_fullStr	The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells
title_full_unstemmed	The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells
title_sort	chemokine receptor cxcr4 and c-met cooperatively promote epithelial-mesenchymal transition in gastric cancer cells
publisher	Elsevier
series	Translational Oncology
issn	1936-5233
publishDate	2018-04-01
description	The C-X-C motif chemokine receptor 4 (CXCR4) pathway can promote tumor metastasis but is dependent on cross talk with other signaling pathways. The MET proto-oncogene (c-MET) participates in metastasis and is highly expressed in gastric cancer. However, the relationship between CXCR4 and c-MET signaling and their mechanisms of action in gastric cancer metastasis remain unclear. In this study, in vitro experiments demonstrated that C-X-C motif chemokine ligand 12 (CXCL12)/CXCR4 induces epithelial-mesenchymal transition (EMT) and promotes migration in gastric cancer cells, which is accompanied by c-MET activation. These phenomena were reversed by c-MET inhibition. Further investigation revealed that c-MET activation correlated with its interaction with caveolin 1 in lipid rafts, induced by CXCL12. In clinical samples, we observed a significant positive association between CXCR4 expression and c-MET phosphorylation (r = 0.259, P = .005). Moreover, samples expressing both receptors were found to indicate significantly poorer patient prognosis (P < .001). These results suggest that CXCL12 induces EMT at least partially through cross talk between CXCR4 and c-MET signaling. In addition, changes in these pathways could have clinical importance for the treatment of gastric cancer.
url	http://www.sciencedirect.com/science/article/pii/S1936523317304199
work_keys_str_mv	AT yucheng thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT yongxisong thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT jingleiqu thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT xiaofangche thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT nasong thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT yibofan thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT tiwen thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT lingxu thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT jinggong thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT xiaoxunwang thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT chenluzhang thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT xiujuanqu thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT yunpengliu thechemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT yucheng chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT yongxisong chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT jingleiqu chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT xiaofangche chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT nasong chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT yibofan chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT tiwen chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT lingxu chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT jinggong chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT xiaoxunwang chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT chenluzhang chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT xiujuanqu chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells AT yunpengliu chemokinereceptorcxcr4andcmetcooperativelypromoteepithelialmesenchymaltransitioningastriccancercells
_version_	1716787585404108800
spelling	doaj-e3ce16d875dc4466b48e59db0e92951a2020-11-24T20:57:47ZengElsevierTranslational Oncology1936-52332018-04-01112487497The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer CellsYu Cheng0Yongxi Song1Jinglei Qu2Xiaofang Che3Na Song4Yibo Fan5Ti Wen6Ling Xu7Jing Gong8Xiaoxun Wang9Chenlu Zhang10Xiujuan Qu11Yunpeng Liu12Department of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR ChinaDepartment of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Address all correspondence to: Xiujuan Qu or Yunpeng Liu, Department of Medical Oncology, Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang 110001, China.Department of Medical Oncology, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China; Address all correspondence to: Xiujuan Qu or Yunpeng Liu, Department of Medical Oncology, Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang 110001, China.The C-X-C motif chemokine receptor 4 (CXCR4) pathway can promote tumor metastasis but is dependent on cross talk with other signaling pathways. The MET proto-oncogene (c-MET) participates in metastasis and is highly expressed in gastric cancer. However, the relationship between CXCR4 and c-MET signaling and their mechanisms of action in gastric cancer metastasis remain unclear. In this study, in vitro experiments demonstrated that C-X-C motif chemokine ligand 12 (CXCL12)/CXCR4 induces epithelial-mesenchymal transition (EMT) and promotes migration in gastric cancer cells, which is accompanied by c-MET activation. These phenomena were reversed by c-MET inhibition. Further investigation revealed that c-MET activation correlated with its interaction with caveolin 1 in lipid rafts, induced by CXCL12. In clinical samples, we observed a significant positive association between CXCR4 expression and c-MET phosphorylation (r = 0.259, P = .005). Moreover, samples expressing both receptors were found to indicate significantly poorer patient prognosis (P < .001). These results suggest that CXCL12 induces EMT at least partially through cross talk between CXCR4 and c-MET signaling. In addition, changes in these pathways could have clinical importance for the treatment of gastric cancer.http://www.sciencedirect.com/science/article/pii/S1936523317304199

The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells

Similar Items