Glioblastoma multiforme (GBM) is the most common and malignant type of central nervous system tumours in adults. Strict regulation of glucose homeostasis has a significant role in GBM pathogenesis. Insulin receptor substrate 1 (IRS1) protein is the most important adaptor molecule involved in the regulation of glucose metabolism. It interacts with many cancer-related receptors and its overexpression is strongly associated with cell proliferation and survival. Our study was aimed to understand the role of IRS1 proteins in GBM cell viability. U-87 MG cells were transfected with pcDNA3.1-flagtagged-human IRS1 expression vector. Insulin induced phosphorylation levels of IRS1, AKT1 and ERK1/2 and Grb2 expression were examined to determine the effects of ectopic IRS1 overexpression on insulin signalling and the viability levels of U-87 MG cells were determined by MTT analysis. Overexpression of IRS1 in U-87 MG cells led to an increase in cell viability. Its overexpression also increased Grb2 expression and phosphorylation of AKT1 through elevation of IRS1 tyrosine phosphorylation in IRS1-transfected U-87 MG cells compared to control and mock transfected groups. Our study showed that increased IRS1 expression and activation may promote the cell viability via AKT1 activation. IRS1 signalling may be considered as a therapeutic target for further studies.

中文翻译：

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胰岛素受体底物1的过表达通过AKT1激活促进胶质母细胞瘤细胞的存活。

多形胶质母细胞瘤（GBM）是成人中最常见和恶性的中枢神经系统肿瘤。葡萄糖稳态的严格调节在GBM发病机理中具有重要作用。胰岛素受体底物1（IRS1）蛋白是参与葡萄糖代谢调节的最重要的衔接子分子。它与许多癌症相关的受体相互作用，其过表达与细胞增殖和存活密切相关。我们的研究旨在了解IRS1蛋白在GBM细胞活力中的作用。用pcDNA3.1-标记的人IRS1表达载体转染U-87 MG细胞。胰岛素引起的IRS1磷酸化水平 检查AKT1和ERK1 / 2和Grb2的表达以确定异位IRS1过表达对胰岛素信号的影响，并通过MTT分析确定U-87 MG细胞的生存能力。U-87 MG细胞中IRS1的过度表达导致细胞活力的增加。与对照组和模拟转染组相比，在IRS1转染的U-87 MG细胞中，它的过表达还通过提高IRS1酪氨酸磷酸化而增加了Grb2表达和AKT1的磷酸化。我们的研究表明，IRS1表达和激活的增加可能通过AKT1激活来促进细胞活力。IRS1信号传导可被视为进一步研究的治疗靶标。与对照组和模拟转染组相比，在IRS1转染的U-87 MG细胞中，它的过表达还通过提高IRS1酪氨酸磷酸化而增加了Grb2表达和AKT1的磷酸化。我们的研究表明，IRS1表达和激活的增加可能通过AKT1激活来促进细胞活力。IRS1信号传导可被视为进一步研究的治疗靶标。与对照组和模拟转染组相比，在IRS1转染的U-87 MG细胞中，它的过表达还通过提高IRS1酪氨酸磷酸化而增加了Grb2表达和AKT1的磷酸化。我们的研究表明，IRS1表达和激活的增加可能通过AKT1激活来促进细胞活力。IRS1信号传导可被视为进一步研究的治疗靶标。