癌癥的重要特點之一是癌細胞的快速分裂和生長,，而這個過程需要大量能量作為支撐，英國研究人員日前發(fā)表報告說,，他們找到了一種能夠限制癌細胞能量來源的方法，可以通過這種方式“餓死”癌細胞,，幫助治療癌癥。
英國帝國理工學院等機構(gòu)研究人員在新一期《自然—細胞生物學》雜志上報告說,，癌細胞通常依靠分解葡萄糖來獲取能量,，如果體內(nèi)的葡萄糖含量不足則轉(zhuǎn)向別的能量來源,，研究人員發(fā)現(xiàn)一種名為NF－kB的蛋白質(zhì)控制著其能量供應方式的轉(zhuǎn)換,，如果抑制這種蛋白質(zhì)的功能,，癌細胞就不能按需轉(zhuǎn)換能量供應方式,，會進入能量供應不足的狀態(tài)甚至“餓死”,。
研究人員在實驗室中用腸癌細胞進行了實驗,，結(jié)果顯示可以通過這種限制能量供應的方式來殺死癌細胞,。此外,，如果在抑制蛋白質(zhì)NF－kB的功能的同時,，使用一種已有的糖尿病藥物二甲雙胍，則“餓死”癌細胞的效率會大大提高,。
領導研究的吉多·弗蘭佐索教授說,，這是首次揭示蛋白質(zhì)NF－kB具有調(diào)節(jié)細胞能量來源的功能，以前雖然也知道它在癌癥中發(fā)揮著某種作用,，但具體機理不是很清楚,，因此與之相關的癌癥治療方式效果也不太理想。本次研究還發(fā)現(xiàn)可以將它和二甲雙胍聯(lián)合使用,，有望在此基礎上研發(fā)出更有效的癌癥治療方式,。(生物谷 Bioon.com)
doi:10.1038/ncb2324
PMC:
PMID:
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.
