孤儿核受体Nur77调控TRAF6/NF-κB信号转导的分子机制及其在炎症相关性肠癌中的作用

我们最近报道了孤儿核受体Nur77与Wnt/β-catenin信号转导在结肠癌中的正负反馈调控机制（FASEB J，2011；Oncogene，2012）。近期我们发现，TRAF6可能是Nur77新型相互作用蛋白，Nur77可参与TRAF6的自泛素化及脂多糖LPS诱导的NF-κB信号转导。基于此，我们提出Nur77介导TRAF6/NF-κB信号转导的改变可能参与调控炎症相关性肠癌的发展进程。本研究以Nur77表达、定位的改变为起始，围绕Nur77/TRAF6相互作用对TRAF6自泛素化修饰、NF-κB信号转导、靶基因表达等方面的影响，阐明Nur77调控TRAF6/NF-κB信号转导的分子机制，并在小鼠炎症性肠癌模型及人炎症相关性肠癌临床组织标本中进行验证，进而明确Nur77/TRAF6/NF-κB信号转导新机制在炎症相关性肠癌发展进程中的作用及临床意义。

We recently reported that these was a regulatory loop between the orphan nuclear receptor Nur77 and Wnt/β-catenin in colon cancer (FASEB J，2011；Oncogene, 2012). Recently, we found that TRAF6 is a candidate of Nur77 interacting protein，and Nur77 is involved in TRAF6 autoubiquitination and LPS-induced NF-κB signal transduction. Base on these findings，We propose a functional association between Nur77 and TRAF6/NF-κB signaling, which will affect inflammation-related colorectal cancer development. On the basis of Nur77 expression and nucleoplasm translocation，we will here try to investigate the effect of Nur77/TRAF6 interaction on TRAF6 autoubiquitination, NF-κB signal transduction and target gene expression, and to clarify the underlying mechanism by which Nur77 regulates TRAF6/NF-κB signaling，which will be confirmed in animal study and clinical samples of Inflammation-related colorectal cancer. Ultimately, We will uncover the potential role and clinical signification of Nur77/TRAF6/NF-κB signaling axis in the development of inflammation-related colorectal cancer .