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此发现无疑为战胜“结肠癌”又迈进一步

作者:微基生物科技(上海)有限公司 2015-06-23T14:31 (访问量:7659)

Critical Role for the DNA Sensor AIM2 in Stem Cell Proliferation and Cancer

由美国St.Jude儿童医院的科学家们发现的一种免疫系统基因在决定结肠癌侵袭性方面的影响引起了广泛关注,基因AIM2缺失会引起小肠细胞增殖而无法控制,与此同时,也影响了肠道菌群的微生态结构,肠道菌群有益的菌群增加会有效预防结肠癌。关于AIM2的这篇文章的发表在国际学术期刊Cell上,这项发现对结肠癌的预防、诊断和治疗上极具重要意义。

许多研究表明AIM2在已患结肠癌的病人中非常常见,研究者只是知道AIM2在免疫系统中具有重要作用,在肿瘤发生机制中没有很好了解,研究人员让小鼠在模拟状态下患癌,同时检测AIM2,发现其功能活性明显下降;研究人员利用遗传学方法降低AIM2功能,再结合其他化合物,实验结果则产生了更多肠道肿瘤,最后研究人员还发现,其AIM2是多功能物质,除了能免疫和抑制小肠干细胞异常扩张外,当AIM2功能异常时对小肠干细胞异常增殖的抑制作用就会解除。

研究者还发现AIM2类似的具有病原感受器功能的分子对于促进健康肠道菌群的形成具有重要作用,

综上:

1.AIM2对小肠干细胞增殖具有调控作用

2.AIM2缺失会影响肠道菌群组成,进而促进结肠癌发生

3.AIM2在免疫系统中发挥重要作用。

Summary

Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune sensor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators was largely intact in Aim2-deficient mice; however, intestinal stem cells were prone to uncontrolled proliferation. Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2. Susceptibility of Aim2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with healthy wild-type mice. These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer. Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer.

原文链接:http://dx.doi.org/10.1016/j.cell.2015.06.001

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