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首页> 外文期刊>The Biochemical Journal >TGF-beta 1 (transforming growth factor-beta 1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity
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TGF-beta 1 (transforming growth factor-beta 1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity

机译:TGF-β1(转化生长因子-β1)介导的胃癌细胞粘附涉及依赖于c-Src活性的Ras / ERK(细胞外信号调节激酶)级联活性的降低

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摘要

Signalling by integrin-mediated cell anchorage to extracellular matrix proteins is co-operative with other receptor-mediated signalling pathways to regulate cell adhesion, spreading, proliferation survival. migration. differentiation and gene expression. It was observed that an anchorage-independent gastric carcinoma cell line (SNU16) became adherent on TGF-beta1 (transforming growth factor beta1)treatment. To undertstand how a signal cross-talk between integrin and TGF-beta1 path ways forms the basis for TGF-beta1 effects, cell adhesion and signalling activities were studied using an adherent subline (SNU16Ad. an adherent variant cell line derived from SNU16) derived from the SNU16 cells. SNU16 and SNU16Ad cells, but not integrin alpha5-expressing SNU16 cells, showed an increase in adhesion on extracellular matrix proteins after TGF-beta1 treatment. This increase was shown to be mediated by an integrin alpha3 subunit. Which Was up-regulated in adherent SNU I 6Ad cells and in TGF-beta1-treated SNU16 cells, compared with the parental SNU16 cells. After TGF-beta1 treatment of SNU I 6Ad cells on fibronectin. Tyr-416 phosphorylation of c-Src was increased, but Ras-GTP loading and ERK1/ERK2 (extra-cellular-signal-regulated kinases 1 and 2) activity were decreased, which showed a dependence on c-Src family kinase activity. Studies on adhesion and signalling activities using pharmacological inhibitors or by transient-transfection approaches showed that inhibition of ERK1/ERK2 activity increased TGF-beta1 mediated cell adhesion slightly, but not the basal cell adhesion significantly, and that c-Src family kinase activity and decrease in Ras/ERKs cascade activity were required for the TGF-beta1 effects. Altogether, the present Study indicates that TGF-beta1 treatment causes anchorage-independent gastric carcinoma cells to adhere by an increase in integrin alpha3 level and a c-Src family kinase activity-dependent decrease in Ras/ERKs cascade activity.
机译:通过整联蛋白介导的细胞锚定到细胞外基质蛋白的信号转导与其他受体介导的信号转导途径协同调节细胞的粘附,扩散,增殖存活。移民。分化和基因表达。观察到不依赖锚固性的胃癌细胞系(SNU16)在TGF-beta1(转化生长因子beta1)治疗上粘附。为了理解整联蛋白和TGF-β1途径之间的信号串扰如何形成TGF-β1效应的基础,使用了源自于细胞的粘附亚系(SNU16Ad。 SNU16细胞。 SNU16和SNU16Ad细胞,但不是表达整合素α5的SNU16细胞,在TGF-beta1处理后显示出对细胞外基质蛋白的粘附增加。该增加表明是由整联蛋白α3亚基介导的。与亲本SNU16细胞相比,它在粘附的SNU I 6Ad细胞和TGF-beta1处理的SNU16细胞中被上调。经过TGF-beta1处理后,纤连蛋白上的SNU I 6Ad细胞出现了变化。 c-Src的Tyr-416磷酸化增加,但Ras-GTP负载和ERK1 / ERK2(细胞外信号调节的激酶1和2)活性降低,这表明对c-Src家族激酶活性的依赖性。使用药理抑制剂或通过瞬时转染方法对粘附和信号传导活性的研究表明,抑制ERK1 / ERK2活性会稍微增加TGF-β1介导的细胞粘附,但不会显着增加基底细胞粘附,并且c-Src家族激酶活性会降低TGF-beta1效应需要Ras / ERKs级联反应。总而言之,本研究表明,TGF-β1处理可通过整合素α3水平的增加和c-Src家族激酶活性依赖性的Ras / ERKs级联活性降低而导致不依赖锚固性的胃癌细胞粘附。

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