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血清和糖皮质激素调节激酶 1(SGK1)是预测非小细胞肺癌不良预后的指标,本研究阐明了 SGK1 抑制剂和γ射线照射处理后 SGK1 的动态变化模式。

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a predictor of poor prognosis in non-small cell lung cancer, and its dynamic pattern following treatment with SGK1 inhibitor and γ-ray irradiation was elucidated.

机构信息

Department of Respiratory Medicine, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 210009, P.R. China.

出版信息

Oncol Rep. 2018 Mar;39(3):1505-1515. doi: 10.3892/or.2018.6181. Epub 2018 Jan 3.

Abstract

The tumor suppressor gene p53 and its dynamic patterns have caused widespread attention in the field of cancer research. Serum and glucocorticoid-regulated kinase 1 (SGK1) with features of serine/threonine kinase activity, which also contributes to the structural and functional similarities with the AKT family of kinases, is a key enzyme in the regulation of immune responses in tumor cells, and SGK1 was noted to be expressed in close relation to p53 protein levels, and there exists a negative feedback pathway between intracellular SGK1 and p53. Noteworthy, SGK1 was detected to play a role in the development of resistance to cancer chemotherapy. In this study, we demonstrated that high SGK1 expression had strong prognostic value for reduced overall survival in NSCLC patients. Detection of SGK1 collectively was helpful to predict the prognosis of NSCLC. We also identified the expression level of SGK1 and the p53 pathway including downstream apoptotic proteins under the stimulation of γ-radiation and SGK1 inhibitor GSK650394, which presented a series of dynamic fluctuations. Our results suggest that SGK1 dynamics could play an important role in cell signaling, which is capable of directly influencing NSCLC cellular fate decisions.

摘要

肿瘤抑制基因 p53 及其动态模式在癌症研究领域引起了广泛关注。血清和糖皮质激素调节激酶 1(SGK1)具有丝氨酸/苏氨酸激酶活性的特征,也与 AKT 激酶家族的结构和功能相似,是肿瘤细胞免疫反应调节的关键酶,并且 SGK1 的表达与 p53 蛋白水平密切相关,细胞内 SGK1 和 p53 之间存在负反馈途径。值得注意的是,SGK1 被检测到在癌症化疗耐药的发展中起作用。在这项研究中,我们证明了高 SGK1 表达对 NSCLC 患者总生存时间降低具有很强的预后价值。检测 SGK1 有助于预测 NSCLC 的预后。我们还在γ辐射和 SGK1 抑制剂 GSK650394 的刺激下,检测了 SGK1 的表达水平和包括下游凋亡蛋白在内的 p53 通路,这些通路呈现出一系列动态波动。我们的研究结果表明,SGK1 动力学可能在细胞信号转导中发挥重要作用,直接影响 NSCLC 细胞命运的决定。

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