PMID- 29494948 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231112 IS - 1936-5233 (Print) IS - 1936-5233 (Electronic) IS - 1936-5233 (Linking) VI - 11 IP - 2 DP - 2018 Apr TI - The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells. PG - 487-497 LID - S1936-5233(17)30419-9 [pii] LID - 10.1016/j.tranon.2018.02.002 [doi] AB - 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. CI - Copyright (c) 2018. Published by Elsevier Inc. FAU - Cheng, Yu AU - Cheng Y AD - 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. FAU - Song, Yongxi AU - Song Y AD - 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. FAU - Qu, Jinglei AU - Qu J AD - 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. FAU - Che, Xiaofang AU - Che X AD - 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. FAU - Song, Na AU - Song N AD - 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. FAU - Fan, Yibo AU - Fan Y AD - 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. FAU - Wen, Ti AU - Wen T AD - 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. FAU - Xu, Ling AU - Xu L AD - 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. FAU - Gong, Jing AU - Gong J AD - 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. FAU - Wang, Xiaoxun AU - Wang X AD - 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. FAU - Zhang, Chenlu AU - Zhang C AD - 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. FAU - Qu, Xiujuan AU - Qu X AD - 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. Electronic address: xiujuanqu@yahoo.com. FAU - Liu, Yunpeng AU - Liu Y AD - 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. Electronic address: ypliu@cmu.edu.cn. LA - eng PT - Journal Article DEP - 20180227 PL - United States TA - Transl Oncol JT - Translational oncology JID - 101472619 PMC - PMC5884220 EDAT- 2018/03/02 06:00 MHDA- 2018/03/02 06:01 PMCR- 2018/02/27 CRDT- 2018/03/02 06:00 PHST- 2017/11/14 00:00 [received] PHST- 2018/01/30 00:00 [revised] PHST- 2018/02/01 00:00 [accepted] PHST- 2018/03/02 06:00 [pubmed] PHST- 2018/03/02 06:01 [medline] PHST- 2018/03/02 06:00 [entrez] PHST- 2018/02/27 00:00 [pmc-release] AID - S1936-5233(17)30419-9 [pii] AID - 10.1016/j.tranon.2018.02.002 [doi] PST - ppublish SO - Transl Oncol. 2018 Apr;11(2):487-497. doi: 10.1016/j.tranon.2018.02.002. Epub 2018 Feb 27.