The Tyrosine Kinase c-Met Contributes to the Pro-tumorigenic Function of the p38 Kinase in Human Bile Duct Cholangiocarcinoma Cells
The Tyrosine Kinase c-Met Contributes to the Pro-tumorigenic Function of the p38 Kinase in Human Bile Duct Cholangiocarcinoma Cells
复制标题
酪氨酸激酶 c-Met 有助于人胆管胆管癌细胞中 p38 激酶的促肿瘤功能
DOI：
10.1074/jbc.m112.406520
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发表时间：
2012-11-16
影响因子：
4.8
通讯作者：
Wang, Hongyang
中科院分区：
文献类型：
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作者：
Dai, Rongyang;Li, Juanjuan;Wang, Hongyang
p38激酶的促肿瘤发生功能在人类胆管癌发生中起关键作用。然而，其内在机制仍然不完全清楚。在这里，我们报告c-Met，肝细胞生长因子（HGF）的酪氨酸激酶受体，有助于p38在人胆管癌细胞中的促肿瘤发生能力。p38和c-Met均能促进人胆管癌细胞的增殖和侵袭。重要的是，p38的抑制或敲低降低了c-Met的基础活化。酪氨酸磷酸酶抑制剂的研究表明，p38促进c-Met的活性，至少在一定程度上，通过抑制受体的去磷酸化。此外，密度增强型磷酸酶-1（DEP-1）参与p38介导的抑制c-Met的去磷酸化。此外，p38抑制c-Met的降解。总之，这些数据提供了一个潜在的机制来解释如何p38促进人胆管癌细胞的增殖和侵袭。我们认为p38和c-Met之间的联系与人胆管癌的进展有关。
Pro-tumorigenic function of the p38 kinase plays a critical role in human cholangiocarcinogenesis. However, the underlying mechanism remains incompletely understood. Here, we report that c-Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), contributes to the pro-tumorigenic ability of p38 in human cholangiocarcinoma cells. Both p38 and c-Met promote the proliferation and invasion of human cholangiocarcinoma cells. Importantly, inhibition or knockdown of p38 decreased the basal activation of c-Met. Tyrosine phosphatase inhibitor studies revealed that p38 promotes the activity of c-Met, at least in part, by inhibiting dephosphorylation of the receptor. Moreover, density enhanced phosphatase-1 (DEP-1) is involved in p38-mediated inhibiting dephosphorylation of c-Met. Furthermore, p38 inhibits the degradation of c-Met. Taken together, these data provide a potential mechanism to explain how p38 promotes human cholangiocarcinoma cell proliferation and invasion. We propose that the link between p38 and c-Met is implicated in the progression of human cholangiocarcinoma.