结直肠癌发生远处转移是患者5年生存率低下的首要原因，其转移的具体调控机制目前尚未完全明确。具有抑癌作用的FOXO4转录因子通过调控相关底物的表达在结直肠癌发生、发展中起重要作用，但其调控结直肠癌转移特别是通过调控结直肠癌干细胞特性影响转移的机制鲜有报道。本课题组前期发现FOXO4表达增加可抑制结直肠癌细胞侵袭转移，并与干性相关基因表达成负相关。同时通过CHIP发现FOXO4可转录调控APC2的表达。本项目拟在前期研究基础上，以“FOXO4-APC2-结直肠癌细胞干性调控及转移”为线索，深入研究FOXO4及其调控蛋白APC2对结直肠癌细胞干性获得的影响，在调控结直肠癌干细胞特性维持中的作用，对结直肠癌EMT及转移的作用，探讨FOXO4与APC2在结直肠癌干细胞调控及转移中的分子机制，寻找相关治疗靶点。为寻找结直肠癌的转移机制以及靶向治疗的可行性提供理论基础。

Metastasis of colorectal cancer(CRC) remains the leading cause of poor 5-year survival rate. Detailed mechanisms regulate metastasis remain unknown. Antioncogenic transcription factor FOXO4 plays important roles in the development and progression of CRC by regulating substrates expression. The potential involvement of FOXO4 in regulating cancer stems cells properties that influencing metastasis in CRC is still not well understood. Our studies have demonstrated that FOXO4 expression could inhibit invasion and metastasis ability of CRC cells and had negative correlation with stemness-related genes expression. We also found by CHIP that the expression of APC2 was regulated by FOXO4. Our further research is to investigate the role of FOXO4 as well as APC2 in regulating stemness acquisition of CRC cells, colorectal cancer stem cell properties maintenance and EMT in CRC, and to explore the molecular regulatory mechanism of FOXO4 and APC2 on regulating stem cell properties and metastasis in CRC. This study also emphasizes on finding the therapeutic target against CRC.