结肠癌干细胞（cCSC）是结肠癌复发转移的种子细胞，其形成与自我更新受炎症微环境调节。阐明该过程的关键分子事件对清除cCSC至关重要。研究表明炎症相关转录因子NFκB可通过CD44和Wnt信号促进干细胞自我更新。申请人发现FOXP3可与NFκB相互作用且抑制NFκB转录活性；而在cCSC中FOXP3的表达降低，过表达FOXP3能抑制干细胞Sphere形成。据此我们推测FOXP3可能是cCSC形成和自我更新的抑制分子。cCSC中FOXP3表达减少导致炎症条件下NFκB活性进一步增强，从而促进cCSC的形成和自我更新。本项目拟首先收集临床标本，分析炎症微环境、FOXP3表达/活化和干细胞自我更新之间的相关性；然后通过干预FOXP3表达，观察炎症条件下cCSC的形成和自我更新能力的变化，并阐明其机制。本项目有望发现一个新的抑制炎症微环境下cCSC形成和自我更新的机制，为清除cCSC提供新靶点。

Colon cancer stem cell (cCSC) is the seed cell of colon cancer initiation and metastasis. Inflammatory microenvironment exert profound influence on the formation and evolution of cCSC. Illustration of the key molecular events in the process would shed light on finding strategies to eradicate the cancer stem cells. Previous studies have shown that NF-κB could promote self-renewal of CSC by enhancing CD44 expression and activating Wnt signaling. Our ongoing study has found that FOXP3 could interact with NF-κB. The expression of FOXP3 in cCSCs is lower than common tumor cells. Overexpression of FOXP3 could inhibit the formation of colon spheres and inhibit NF-κB activaty. To this end, we hypothesized that FOXP3 may inhibit the formation and self-renewal capacity of colon cancer stem cells. The reduced expression of FOXP3 leads to inhibition of NF-κB activity and hence promoting formation and self-renewal of colon stem cell in inflammation. This project will first analyze the correlation of intensity of inflammation, the expression of FOXP3 and self-renewal capacity of colon stem cell. Then, we will further confirm whether FOXP3 plays an essential role in formation and self-renewal of cCSC under inflammation. It is highly possible that we would discover a novel mechanism how cells themselves inhibit cCSC self-renewal under inflammatory microenvironment, and thus providing a new target for the removal of colon cancer stem cells.