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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >COUP-TFII Knock-down Promotes Proliferation and Invasion in Colorectal Cancer Cells via Activation of Akt Pathway and Up-regulation of FOXC1
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COUP-TFII Knock-down Promotes Proliferation and Invasion in Colorectal Cancer Cells via Activation of Akt Pathway and Up-regulation of FOXC1

机译:通过AKT途径和富索升压,COUP-TFII淘汰降低促进结肠直肠癌细胞的增殖和侵袭和FOXC1的上调

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摘要

Background/Aim: The chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) regulates cancer cell proliferation and invasion via complex molecular mechanisms. We aimed to investigate whether COUP-TFII modulates proliferation and invasion of the colorectal adenocarcinoma cell line HT-29. Materials and Methods: HT-29 cells were stably tranfected with COUPTFII shRNA plasmid to knock-down COUP-TFII (COUPTFII shRNA-HT-29 cells). Cell proliferation, colony formation assay, invasion assay, microarray assays and western blot analyses were performed. Results: Cell proliferation and invasion were significantly enhanced in COUP-TFII shRNA-HT-29 cells. The protein levels of forkhead box C1 (FOXC1), p-Akt, p-glycogen synthase kinase-3 beta (p-GSK-3 beta), and beta-catenin, which are known to be involved in cell proliferation and invasion, were significantly increased in COUP-TFII shRNA-HT-29 cells. Akt inhibitor IV and dominant negative (DN)-Akt expression vector transfection reversed the increased proliferation and invasion, which was accompanied by decreased protein levels of p-Akt, p-GSK-3 beta, beta-catenin and FOXC1. Conclusion: COUP-TFII knock-down promoted proliferation and invasion via activation of Akt/GSK-3 beta/beta-catenin and upregulation of FOXC1. Further studies on the molecular mechanism of interaction between beta-catenin and FOXC1 expression may reveal novel target molecules for metastatic colorectal cancer therapy.
机译:背景/目的:鸡卵黄明升起启动子转录因子II(COUP-TFII)通过复杂的分子机制调节癌细胞增殖和侵袭。我们旨在调查COUP-TFII是否调节结直肠腺癌细胞系HT-29的增殖和侵袭。材料和方法:将HT-29细胞与CupptFII shRNA质粒稳定地捕获到敲除Coup-TFII(Couptfii shRNA-HT-29细胞)。进行细胞增殖,菌落形成测定,侵袭测定,微阵列测定和蛋白质印迹分析。结果:COUP-TFII shRNA-HT-29细胞中细胞增殖和侵袭显着增强。众所周知,蛋白质水平的叉头箱C1(FoxC1),p-Akt,p-糖原合酶激酶-3β(p-GSK-3β)和β-连环蛋白的蛋白质COUP-TFII shRNA-HT-29细胞显着增加。 AKT抑制剂IV和显性负(DN)-AKT表达载体转染反转增加的增殖和侵袭,伴随P-AKT,P-GSK-3β,β-连环蛋白和FOXC1的蛋白质水平降低。结论:通过激活AKT / GSK-3β-Catenin和FoxC1的上调,Coup-TFII淘汰促进促进增殖和侵袭。进一步研究β-连环蛋白和FOXC1表达之间的相互作用的分子机制可以揭示用于转移结直肠癌治疗的新型靶分子。

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