癌症的重要特点之一是癌细胞的快速分裂和生长,而这个过程需要大量能量作为支撑,英国研究人员日前发表报告说,他们找到了一种能够限制癌细胞能量来源的方法,可以通过这种方式“饿死”癌细胞,帮助治疗癌症。
英国帝国理工学院等机构研究人员在新一期《自然—细胞生物学》杂志上报告说,癌细胞通常依靠分解葡萄糖来获取能量,如果体内的葡萄糖含量不足则转向别的能量来源,研究人员发现一种名为NF-kB的蛋白质控制着其能量供应方式的转换,如果抑制这种蛋白质的功能,癌细胞就不能按需转换能量供应方式,会进入能量供应不足的状态甚至“饿死”。
研究人员在实验室中用肠癌细胞进行了实验,结果显示可以通过这种限制能量供应的方式来杀死癌细胞。此外,如果在抑制蛋白质NF-kB的功能的同时,使用一种已有的糖尿病药物二甲双胍,则“饿死”癌细胞的效率会大大提高。
领导研究的吉多·弗兰佐索教授说,这是首次揭示蛋白质NF-kB具有调节细胞能量来源的功能,以前虽然也知道它在癌症中发挥着某种作用,但具体机理不是很清楚,因此与之相关的癌症治疗方式效果也不太理想。本次研究还发现可以将它和二甲双胍联合使用,有望在此基础上研发出更有效的癌症治疗方式。(生物谷 Bioon.com)
doi:10.1038/ncb2324
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NF-[kappa]B controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration
Claudio Mauro; Shi Chi Leow; Elena Anso; Sonia Rocha; Anil K. Thotakura; Laura Tornatore; Marta Moretti; Enrico De Smaele; Amer A. Beg; Vinay Tergaonkar; Navdeep S. Chandel; Guido Franzoso
Cell proliferation is a metabolically demanding process1, 2. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth1, 2. NF-κB/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis3, but whether NF-κB regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-κB organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-κB inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-κB inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-κB-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2; ref. 4). Our findings identify NF-κB as a physiological regulator of mitochondrial respiration and establish a role for NF-κB in metabolic adaptation in normal cells and cancer.