Analysis of the molecular mechanisms by which CDX2 supresses colon caner cell proliferation

CDX2是一种同源盒转录因子，在肠上皮细胞中特异性表达。我们先前已经使用基因敲除小鼠模型表明CDX2抑制结肠肿瘤发生。在这项研究中，我们发现CDX2通过其非转录功能抑制结肠癌细胞的增殖，而它作为一个转录因子。CDX2对细胞增殖的抑制作用部分是通过增加CDK抑制剂p27蛋白的水平来介导的。此外，我们发现泛素E1样酶ATG7作为与CDX2相互作用的蛋白质，并且CDX2刺激自噬。有趣的是，CDX2通过自噬诱导一种细胞死亡。这些结果表明，CDX2通过ATG7介导的自噬刺激抑制结肠肿瘤的发生。

CDX2 is a homebox transcription factor that is expressed specifically in the intestinal epithelial cells. We have previously shown that CDX2 supresses colonic tumorigensis, using a knockout mouse model. In this study, we have found that CDX2 suppresses proliferation of colon cancer cells through its non-transcriptional function, wheares it acts as a transcription factor. The block of cell proliferation caused by CDX2 is mediated partilly through increased level of p27 protein, a CDK inhibitor. In addition, we have found ubiqutin E1-like enzyme ATG7 as a protein interacting with CDX2, and that CDX2 stimulates autophagy. Interestingly, CDX2 induces a kind of cell death through autophagy. Thease results have suggested that CDX2 suppresses colonic tumorigensis through ATG7-mediated stimulation of autophagy.