结直肠癌（CRC）在全球具有高的发病率和致死率，亟需寻找新的分子标记物来协助诊治。研究表明许多调控胚胎干细胞的蛋白在肿瘤中也具有重要作用。我们近期发现蛋白Actl6a能维持小鼠胚胎干细胞自我更新，并通过数据库分析发现ACTL6A在CRC中高表达。预实验进一步证明降低ACTL6A会显著抑制CRC细胞增殖，并导致ERK磷酸化水平下调，提示ACTL6A可能调控ERK通路并影响CRC发生发展。本项目拟利用免疫组化、Western blot等检测ACTL6A在CRC临床组织的表达；通过过表达及RNAi技术，结合细胞与蛋白实验研究ACTL6A在CRC中的作用；利用免疫共沉淀、荧光素酶实验及芯片技术等阐明ACTL6A下游调控靶点和通路；最终通过小鼠荷瘤实验和临床标本验证ACTL6A及下游通路的表达及与CRC发生发展相关性。本研究将阐明ACTL6A在CRC中的作用及机制，为CRC诊疗提供新的思路和方法。

Identifying new prognostic biomarkers that can predict outcome of colorectal cancer could contribute significantly to the treatment in CRC patients. We found that Actl6a could maintain Stem Cell pluripotency. We found that ACTL6A is high express in colorectal cancer and Actl6a can increase phosphorylation of ERK. Therefore, we propose a hypothesis that“Actl6a regulate ERK and colorectal cancer development”. In this study, we will explore the function of Actl6a in CRC by protein overexpression or RNAi-mediated downregulation assays; COIP and point mutation was used to find the binding site of Actl6a and ERK. Luciferase assay to investigate the mechanism of regulation of ERK by Actl6a. By using in vivo and in vitro experiments, we could study the role of Actl6a in CRC from multi-levels. Our study will provide basic knowledge for future therapy of the Actl6a signaling pathway.