12月12日，法國國家科研中心發(fā)表公報說,，法研究人員日前發(fā)現(xiàn)一個名為DCC的基因可通過誘導(dǎo)癌細(xì)胞凋亡來抑制結(jié)腸和直腸癌發(fā)展，從而起到預(yù)防和治療癌癥的效果,。
這項研究由法國國家科研中心等機構(gòu)共同完成,。領(lǐng)導(dǎo)該研究的法國專家帕特里克·梅倫和同事在英國《自然》雜志網(wǎng)站上報告說，他們發(fā)現(xiàn)DCC基因的活動可啟動“依賴性受體”機制,，該機制可通過誘導(dǎo)癌細(xì)胞死亡來預(yù)防癌癥,。
比如，當(dāng)DCC基因通過正常表達,，阻止其指導(dǎo)合成的受體蛋白質(zhì)與神經(jīng)軸突導(dǎo)向分子netrin-1結(jié)合,，相關(guān)細(xì)胞就會收到誘導(dǎo)死亡信號，隨后該細(xì)胞逐漸凋亡,。但如果DCC基因無法正常表達,，導(dǎo)致上述受體蛋白質(zhì)與神經(jīng)軸突導(dǎo)向分子相互結(jié)合，有關(guān)細(xì)胞就會繼續(xù)存活,，甚至異常增殖,。
法國研究者通過老鼠實驗發(fā)現(xiàn),，如果老鼠的DCC基因由于變異而喪失表達功能，那么這種老鼠會患上結(jié)腸癌,。
帕特里克·梅倫說,，人體可通過DCC基因啟動的“依賴性受體”機制來抑制癌細(xì)胞增殖并預(yù)防癌癥，但一些癌細(xì)胞可以阻斷“依賴性受體”機制,，從而不受控制,。這一發(fā)現(xiàn)有望指引新療法研發(fā)，通過誘導(dǎo)癌細(xì)胞凋亡來治療癌癥,。
據(jù)帕特里克·梅倫介紹,，其研究團隊已經(jīng)研制出幾種能激發(fā)DCC基因并誘導(dǎo)癌細(xì)胞凋亡的藥物，在一些動物身上已試驗成功,，希望3年后能對這些藥物進行臨床試驗,。（生物谷Bioon.com）
doi:10.1038/nature10708
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DCC constrains tumour progression via its dependence receptor activity
Marie Castets, Laura Broutier, Yann Molin, Marie Brevet, Guillaume Chazot, Nicolas Gadot, Armelle Paquet, Laetitia Mazelin, Loraine Jarrosson-Wuilleme, Jean-Yves Scoazec, Agnès Bernet & Patrick Mehlen
The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers1 and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development3. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis.
