The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells.
The Chemokine Receptor CXCR4 and c-MET Cooperatively Promote Epithelial-Mesenchymal Transition in Gastric Cancer Cells.
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DOI：
10.1016/j.tranon.2018.02.002
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发表时间：
2018-04
影响因子：
5
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Cheng Y;Song Y;Qu J;Che X;Song N;Fan Y;Wen T;Xu L;Gong J;Wang X;Zhang C;Qu X;Liu Y
C-X-C基序趋化因子受体4（CXCR 4）通路可以促进肿瘤转移，但依赖于与其他信号通路的串扰。MET原癌基因（c-MET）参与转移，在胃癌中高表达。然而，CXCR 4和c-MET信号传导之间的关系及其在胃癌转移中的作用机制仍不清楚。在这项研究中，体外实验证明C-X-C基序趋化因子配体12（CXCL 12）/CXCR 4诱导上皮间质转化（EMT）并促进胃癌细胞的迁移，这伴随着c-MET活化。这些现象被c-MET抑制逆转。进一步的研究表明，c-MET的激活与CXCL 12诱导的脂筏中caveolin 1的相互作用相关。在临床样本中，我们观察到CXCR 4表达与c-MET磷酸化之间存在显著正相关（r = 0.259，P = .005）。此外，发现表达两种受体的样品指示显著较差的患者预后（P <0.001）。这些结果表明，CXCL 12至少部分通过CXCR 4和c-MET信号传导之间的串扰诱导EMT。此外，这些途径的变化可能对胃癌的治疗具有临床意义。
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.
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