德國(guó)維爾茨堡大學(xué)與亥姆霍茲大研究中心聯(lián)合會(huì)傳染病研究中心的研究人員合作研究,，發(fā)現(xiàn)了癌細(xì)胞的“阿基里斯之踵”,，其相關(guān)研究成果已在《自然》雜志上發(fā)布,。新的癌癥治療方法的基本機(jī)制是：在關(guān)閉癌細(xì)胞內(nèi)部的能量監(jiān)控機(jī)制后,，癌細(xì)胞將無(wú)視內(nèi)部的新陳代謝需要繼續(xù)分裂繁殖,，最終因缺乏足夠能量供應(yīng)而死亡,。制藥企業(yè)已經(jīng)對(duì)該技術(shù)方案表示出極大興趣,。
根據(jù)德國(guó)癌癥援助協(xié)會(huì)發(fā)布的統(tǒng)計(jì)數(shù)字：德國(guó)每年新增約49萬(wàn)癌癥患者,，而同期約有21.8人死于癌癥。專家預(yù)測(cè)到2050年該數(shù)字還將會(huì)提高約30%,。目前,，對(duì)于癌癥常見(jiàn)的治療方式是放療和化療，通過(guò)放療和化療來(lái)阻止癌細(xì)胞繼續(xù)生長(zhǎng),。此次,，德國(guó)維爾茨堡大學(xué)的研究人員卻采取了全新研究思路：讓癌細(xì)胞無(wú)節(jié)制生長(zhǎng)直至死亡，而其基礎(chǔ)理論就是簡(jiǎn)單的后勤供應(yīng)問(wèn)題,。
與其他身體細(xì)胞一樣,，癌細(xì)胞存活生長(zhǎng)就要從營(yíng)養(yǎng)物質(zhì)中不斷獲取能量。一方面用于細(xì)胞自身生成發(fā)育,，另一方面用于細(xì)胞分裂繁殖,。此外，還要保障細(xì)胞內(nèi)部的基本新陳代謝,。研究人員在研究關(guān)閉特定的酶對(duì)癌癥細(xì)胞反應(yīng)過(guò)程中,，發(fā)現(xiàn)了具有資源管理功能的一種“監(jiān)控分子酶”。當(dāng)有足夠的能量ATP情況下,，癌細(xì)胞自身生長(zhǎng)發(fā)育和分裂繁殖過(guò)程是平衡的,。當(dāng)能量ATP稀缺情況下，監(jiān)控分子酶將通過(guò)調(diào)節(jié)機(jī)制首先確保癌細(xì)胞自身基本新陳代謝的能量需求,，從而實(shí)現(xiàn)自我保護(hù)的目標(biāo),。為此，在能量稀缺情況下,，癌細(xì)胞如果無(wú)法從監(jiān)控分子酶獲取能量平衡反饋信息時(shí),，它們將繼續(xù)浪費(fèi)大量能量資源進(jìn)行分裂繁殖活動(dòng)。最終會(huì)因?yàn)槟芰抗?yīng)不足而自我死亡,。
研究人員把這種監(jiān)控分子酶稱為Ark5酶,，這種酶就好比是癌細(xì)胞的“阿基里斯之踵”，可以作為治療癌癥的新藥物。研究人員已成功在實(shí)驗(yàn)鼠體內(nèi)進(jìn)行了測(cè)試,，證實(shí)其可以有效抑制和縮小實(shí)驗(yàn)鼠體內(nèi)的肝腫瘤,。目前實(shí)驗(yàn)顯示該方法在實(shí)驗(yàn)動(dòng)物體內(nèi)可以有效對(duì)抗結(jié)腸癌和肝癌細(xì)胞，對(duì)其它癌細(xì)胞是否有效還有待研究,。此外,，研究人員還驚奇發(fā)現(xiàn)，監(jiān)控分子酶失去活性對(duì)于普通健康細(xì)胞沒(méi)有任何影響,，其具體原因還有待進(jìn)一步研究,。當(dāng)然，研究人員和制藥企業(yè)更看重的是其未來(lái)用于治療癌癥的巨大潛力,。(生物谷：Bioon.com)
doi: 10.1038/nature10927
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Deregulated MYC expression induces dependence upon AMPK-related kinase 5
Lidan Liu,1, 7 Jannes Ulbrich,1, 7 Judith Müller,1, 8 Torsten Wüstefeld,2, 3 Lukas Aeberhard,4, 8 Theresia R. Kress,1, 8 Nathiya Muthalagu,1 Lukas Rycak,5 Ramona Rudalska,2 Roland Moll,6 Stefan Kempa,4 Lars Zender,2, 3 Martin Eilers1 & Daniel J. Murphy1
Deregulated expression of the MYC oncoprotein contributes to the genesis of many human tumours, yet strategies to exploit this for a rational tumour therapy are scarce. MYC promotes cell growth and proliferation, and alters cellular metabolism to enhance the provision of precursors for phospholipids and cellular macromolecules1, 2. Here we show in human and murine cell lines that oncogenic levels of MYC establish a dependence on AMPK-related kinase 5 (ARK5; also known as NUAK1) for maintaining metabolic homeostasis and for cell survival. ARK5 is an upstream regulator of AMPK and limits protein synthesis via inhibition of the mammalian target of rapamycin 1 (mTORC1) signalling pathway. ARK5 also maintains expression of mitochondrial respiratory chain complexes and respiratory capacity, which is required for efficient glutamine metabolism. Inhibition of ARK5 leads to a collapse of cellular ATP levels in cells expressing deregulated MYC, inducing multiple pro-apoptotic responses as a secondary consequence. Depletion of ARK5 prolongs survival in MYC-driven mouse models of hepatocellular carcinoma, demonstrating that targeting cellular energy homeostasis is a valid therapeutic strategy to eliminate tumour cells that express deregulated MYC.
