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首页> 外文期刊>Cell biology international. >Glucose regulates heat shock factor 1 transcription activity via mTOR pathway in HCC cell lines
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Glucose regulates heat shock factor 1 transcription activity via mTOR pathway in HCC cell lines

机译:葡萄糖通过HCC细胞系中的mTOR途径调节热休克因子1的转录活性

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摘要

HSF1-mediated heat shock response is activated in most tumors and plays important roles in regulating tumor homeostasis. However, the signals underlying HSF1 activation is still not completely understood. In this paper, we find that glucose, the dominant tumor energy supplement, participates in regulating HSF1's activation in HCC cell lines. The immunoblotting results indicate that the phosphorylation of HSF1/S326, a hallmark of HSF1 activation, varies between the HCC cell lines (e.g., SMMC7721, HapG2, plc/prf5, and Chang-liver). Glucose, but not 2D-glucose, can induce the phosphorylation of HSF1 at S326 and upregulate the expression of HSF1's downstream alpha B-crystallin and Hsp70 as well as the none-heat shock proteins CSK2 and RBM23 in two tested hepatocellular carcinoma cell lines (prl/prf5 and SMMC7721). Rapamycin, an inhibitor of mTOR, can suppress the glucose-induced phosphorylation of HSF1/S326 and the expression of alpha B-crystallin. Knockdown of HSF1 with shRNA enhances the glucose-depletion-mediated inhibition of plc/prf5 cell proliferation. Our data reveal that HSF1 can be activated by glucose-mTOR pathway, providing an alternative pathway for targeting HSF1 in tumor therapy.
机译:HSF1介导的热休克反应在大多数肿瘤中均被激活,并在调节肿瘤稳态中起重要作用。但是,仍未完全了解HSF1激活的基础信号。在本文中,我们发现葡萄糖是主要的肿瘤能量补充剂,参与调节HCC细胞系中HSF1的活化。免疫印迹结果表明,HSF1 / S326的磷酸化(HSF1激活的标志)在HCC细胞系(例如SMMC7721,HapG2,plc / prf5和Chang-liver)之间发生变化。葡萄糖而不是2D葡萄糖可以诱导S326处HSF1的磷酸化,并在两个经过测试的肝癌细胞系中上调HSF1的下游αB-晶状蛋白和Hsp70以及非热休克蛋白CSK2和RBM23的表达(prl / prf5和SMMC7721)。雷帕霉素是mTOR的抑制剂,可以抑制葡萄糖诱导的HSF1 / S326磷酸化和αB-晶状体蛋白的表达。用shRNA敲低HSF1可以增强葡萄糖消耗介导的plc / prf5细胞增殖的抑制作用。我们的数据表明,HSF1可以被葡萄糖-mTOR途径激活,为肿瘤治疗中靶向HSF1提供了另一种途径。

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