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

Translational Oncology
Yu ChengYunpeng Liu

Abstract

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 im...Continue Reading

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Citations

Oct 27, 2018·International Journal of Molecular Sciences·Hongli ZhangYan-Dong Wang
Dec 1, 2019·Expert Opinion on Investigational Drugs·Helena OliveresJoan Maurel
Jan 17, 2021·International Journal of Molecular Sciences·Michela CodiniElisabetta Albi
Dec 25, 2019·Seminars in Cancer Biology·Sara K DanielVenu G Pillarisetty
May 8, 2021·Cancer Metastasis Reviews·Sugandha Saxena, Rakesh K Singh
Nov 14, 2020·International Journal of Molecular Sciences·Elzbieta PawluczukBarbara Mroczko

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Methods Mentioned

BETA
ELISA
Immunoprecipitation
electrophoresis
Assay

Software Mentioned

SPSS

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