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

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

Translational Oncology (Apr 2018)

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

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

Affiliations

Yu Cheng: 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
Yongxi Song: Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, PR China
Jinglei Qu: 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
Xiaofang Che: 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
Na Song: 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
Yibo Fan: 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
Ti Wen: 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
Ling Xu: 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
Jing Gong: 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
Xiaoxun Wang: 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
Chenlu Zhang: 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
Xiujuan Qu: 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.
Yunpeng Liu: 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.

Journal volume & issue: Vol. 11, no. 2
pp. 487 – 497

Abstract

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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.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

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