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Crosstalk between TF/FVIIa and EGFR signaling in colorectal cancer cells

机译:TF / FVIIA和EGFR信号在结肠直肠癌细胞之间的串扰

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TF/FVIIa (Tissue Factor/Active Coagulation factor VII) and EGFR (Epidermal Growth Factor Receptor) signaling both promote malignant progression of colorectal cancer. However, the crosstalk of these two signaling pathways in human colorectal cancer cells remains unclear. Here we detected the changes of mRNA profile in human colorectal cancer cell SW620 exposed to FVIIa. Microarray showed that mRNA levels of EGFR ligands were significantly upregulated. Western blot analysis confirmed the upregulation of EGFR ligands and the phosphorylation of EGFR at tyrosine-845 in colorectal cancer cells exposed to FVIIa. However, knockdown of TF by RNAi could block the upregulation of EGFR ligands induced by FVIIa stimulation. On the other hand, the expression of components of TF/FVIIa signaling was significantly upregulated in LoVo cells stimulated by EGF. However, the crosstalk between the two signaling pathways could not be detected in HT-29 colon cancer cells bearing wild-type KRAS. Taken together, our study suggest that the crosstalk between TF/FVIIa and EGFR signaling pathways in colon cancer cells depends on KRAS mutation.
机译:TF / FVIIA(组织因子/活性凝血因子VII)和EGFR(表皮生长因子受体)信号传导促进结肠直肠癌的恶性进展。然而,在人结肠直肠癌细胞中这两个信号传导途径的串扰仍不清楚。在这里,我们检测到暴露于FVIIa的人结肠直肠癌细胞SW620中mRNA谱的变化。微阵列显示,EGFR配体的mRNA水平显着上调。 Western印迹分析证实了EGFR配体的上调和EGFR在暴露于FVIIa的结肠直肠癌细胞中的EGFR磷酸化。然而,RNAI的TF敲低可以阻断FVIIA刺激诱导的EGFR配体的上调。另一方面,在EGF刺激的Lovo细胞中显着上调TF / FVIIA信号传导组分的表达。然而,在含有野生型KRA的HT-29结肠癌细胞中无法检测到两个信号传导途径之间的串扰。我们的研究表明,结肠癌细胞中TF / FVIIA和EGFR信号通路之间的串扰取决于KRAS突变。

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