Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential
Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential
复制标题
DOI：
10.1038/sj.onc.1201496
复制
发表时间：
1997-12-18
期刊：
影响因子：
8
通讯作者：
Yeatman, TJ
中科院分区：
文献类型：
--
作者：
Mao, WG;Irby, R;Yeatman, TJ
最近的数据表明信号转导可能在转移表型的发展和调节中发挥关键作用。在这里，我们研究了c-Src激活在人结肠癌肝脏转移过程中的作用，我们的数据来自两组不同的人结肠癌细胞系转移变体，表明与低转移细胞相比，高转移细胞不仅表现出组成性升高的c-Src蛋白激酶活性，而且受体酪氨酸激酶参与配体激活 c-Src 高于基础水平。具体来说，表皮生长因子受体（EGFR）、p185HER2/Neu和肝细胞生长因子受体（c-Met）似乎与该过程有关，因为它们优先激活高度转移细胞中的c-Src，EGFR被发现与结肠癌细胞中的c-Src相关，并且EGFR的特异性抑制剂导致c-Src活性降低至基础水平。此外，c-Src 转染子显示出部分激活的 EGFR，表明 c-Src 在 EGFR 调节中具有反馈作用。 EGFR 配体激活后，c-Src 的免疫复合物中也发现了 p185HER2/Neu，但仅在高度转移的细胞中。总的来说，这些观察结果表明，c-Src 以催化方式与多种细胞表面生长因子相互作用，从而促进具有转移潜力的肿瘤细胞的发育。
Recent data suggest that signal transduction may have a critical role in the development and regulation of the metastatic phenotype. Here, we investigated the role of c-Src activation in the process of human colon cancer metastasis to the Liver, Our data, derived from two different sets of human colon cancer cell line metastatic variants, suggest that not only do highly-metastatic cells display constitutively elevated c-Src protein kinase activity when compared to poorly metastatic cells, but also that receptor tyrosine kinases participate in the ligand-activation of c-Src above basal levels. Specifically, the epidermal growth factor receptor (EGFR), p185HER2/Neu and the hepatocyte growth factor receptor (c-Met) appear to be Linked to the process because they preferentially activate c-Src in highly-metastatic cells, EGFR was found to associate with c-Src in colon cancer cells and specific inhibitors of the EGFR resulted in a reduction of c-Src activity to basal levels. In addition, c-Src transfectants displayed partially-activated EGFRs, suggesting a feedback role for c-Src in the regulation of the EGFR. p185HER2/Neu was also identified in immunocomplexes of c-Src following Ligand activation of the EGFR, but only in highly-metastatic cells, Collectively, these observations suggest a paradigm whereby c-Src interacts with multiple cell-surface growth factors in a catalytic fashion for the development of tumor cells with metastatic potential.