AMP-kinase mediates adaptation of glioblastoma cells to conditions of the tumour microenvironment

Proteomic analysis of LNT-299 cells.In this experimental study, we investigated the role of the AMPK-mediated stress response in human GB cells. Mimicking the conditions of the tumour microenvironment we deprived GB cells of glucose and oxygen to characterize metabolic effects and to delineate the relevance of potential downstream targets. AMPK inhibition was modelled by using double-knockout cells of the catalytic subunits α1 and α2. We here report that AMPK activation promotes GB cell survival in the context of both hypoxia and glucose starvation by promoting metabolic adaptation. Furthermore, we found that knockout of the catalytic AMPK subunits resulted in an impaired tumour formation and prolonged survival in vivo. Taken together, the results of this study indicate that the use of AMPK inhibitors could be beneficial to improve GB therapy strategies.

LNT-299细胞的蛋白质组学分析。本实验研究旨在探究腺苷酸活化蛋白激酶（AMPK）介导的应激反应在人胶质母细胞瘤（GB）细胞中的作用。本研究通过模拟肿瘤微环境条件，对GB细胞实施葡萄糖与氧剥夺处理，以表征其代谢效应，并阐明潜在下游靶点的相关性。通过构建催化亚基α1与α2双敲除细胞，建立AMPK抑制模型。本研究结果显示，AMPK激活可通过促进代谢适应，在缺氧与葡萄糖饥饿双重应激条件下提升GB细胞的存活率。此外，本研究发现敲除AMPK催化亚基会在体内损害肿瘤形成能力，并延长受试个体的生存期。综上，本研究结果表明，使用AMPK抑制剂或可优化胶质母细胞瘤的治疗策略。