LIM蛋白AJUBA参与调控基因转录、细胞分化、增殖、迁移与粘附等多种生物学功能。本项目发现AJUBA表达水平与结肠癌细胞的恶性程度呈正相关，且AJUBA在临床结直肠癌组织中高表达。可见AJUBA与结肠癌的关系密不可分。为深入研究其作用机制，我们对AJUBA敲低的结肠癌细胞系进行表达谱分析，发现一系列干扰素诱导基因的表达受到影响，其中已证实促凋亡蛋白IFIT2的上调。IFIT2是JAK-STAT通路中的下游靶基因。我们初步发现AJUBA可抑制STAT1的磷酸化及入核。我们将展开如下研究：1)明确IFIT2是AJUBA抗凋亡和促进肿瘤发展的下游分子。2)阐明AJUBA是否通过JAK/STAT信号调控IFIT2及分子机制。3)分析临床样本中IFIT2与AJUBA的相关性，探寻新的结直肠癌诊断标志物及治疗靶点。期望通过研究AJUBA调控结直肠癌发展的下游分子机制，为其临床治疗提供新的理论基础。

The LIM protein AJUBA functions as scaffold, which participates in the assembly of multiple protein complexes and involves in different kinds of biological processes such as mitosis, gene transcription, cell adhesion, differentiation, proliferation and migration. In this study, we found that the expression of AJUBA was positive correlated with the malignancy of colorectal cancer cell lines. Knockdown of AJUBA results in the apoptosis of colorectal cancer cell. And also, AJUBA was highly expressed in the clinical specimens of colorectal cancer. Therefore, we proposed that AJUBA had vital roles in colorectal cancer development. In order to demonstrate the mechanism of AJUBA in the progression of colorectal cancer, we use gene expression profile analysis to explore the potential target proteins of AJUBA in colorectal cancer by comparing AJUBA knockdown and normal cells. We found that knockdown of AJUBA had significantly effects on almost all of the Interferon-Stimulated (ISG) genes, including the apoptosis-inducing protein IFIT2 which was regulated by JAK/STAT signaling. The higher expression of IFIT2 in AJUBA knockdown cell was confirmed by real-time PCR and western blotting. Interestingly, we found that AJUBA could block STAT1 phosphorylation and translocation from cytoplasm into nucleus. Thus, this project would focus on demonstrating the roles of AJUBA in the progression of colorectal cancer. In this project, 1) we would illuminate if IFIT2 is the potential target of AJUBA in regulating cell apoptosis and colorectal cancer development. 2) we would define if AJUBA regulating IFIT2 expression through JAK/STAT signaling pathway. 3) we would explore if AJUBA could be used as diagnostic marker for colorectal cancer by analysis the clinical specimens. In conclusion, this project presented here would hopefully illuminate the functions and molecular mechanism of AJUBA in regulating cell apoptosis and colorectal cancer development. This study is likely to highlight a new path to develop anti-tumor drugs for colorectal cancer.