法国国家科研中心12月12日发表公报说，法研究人员日前发现一个名为DCC的基因可通过诱导癌细胞凋亡来抑制结肠和直肠癌发展，从而起到预防和治疗癌症的效果。
这项研究由法国国家科研中心等机构共同完成。领导该研究的法国专家帕特里克•梅伦和同事在英国《自然》杂志网站上报告说，他们发现DCC基因的活动可启动“依赖性受体”机制，该机制可通过诱导癌细胞死亡来预防癌症。
比如，当DCC基因通过正常表达，阻止其指导合成的受体蛋白质与神经轴突导向分子netrin-1结合，相关细胞就会收到诱导死亡信号，随后该细胞逐渐凋亡。但如果DCC基因无法正常表达，导致上述受体蛋白质与神经轴突导向分子相互结合，有关细胞就会继续存活，甚至异常增殖。
法国研究者通过老鼠实验发现，如果老鼠的DCC基因由于变异而丧失表达功能，那么这种老鼠会患上结肠癌。
帕特里克•梅伦说，人体可通过DCC基因启动的“依赖性受体”机制来抑制癌细胞增殖并预防癌症，但一些癌细胞可以阻断“依赖性受体”机制，从而不受控制。这一发现有望指引新疗法研发，通过诱导癌细胞凋亡来治疗癌症。
据帕特里克•梅伦介绍，其研究团队已经研制出几种能激发DCC基因并诱导癌细胞凋亡的药物，在一些动物身上已试验成功，希望3年后能对这些药物进行临床试验。
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, 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.
文献链接：https://www.nature.com/nature/journal/vaop/ncurrent/full/nature10708.html
