作为p53靶基因Killin，其启动子的甲基化与Cowden综合征，乳腺癌和甲状腺癌等多种癌症的发生紧密相关。关于Killin抑癌机制，较深入的认识主要有其高亲和性结合并抑制DNA合成，并与细胞周期S期和G2期阻滞相关。近年来，项目组研究发现Killin抑制肿瘤发生与其在细胞G1期中的功能紧密相关，Killin能通过上调p21而参与p53介导的G1期阻滞。然而，关于Killin在p53介导的G1期阻滞中具体作用机制尚不明确。因此，本项目拟在前期研究基础上开展三个方面的研究：1）鉴定Killin在p53介导的G1期阻滞中的功能；2）揭示p53→Killin→p21→G1期阻滞的分子机制；3）探究临床结肠癌样本中Killin与p21表达的相关性，及其与肿瘤恶性程度的关系。此项研究有望阐明Killin通过参与p53介导的G1期阻滞而抑制肿瘤发生的新机制，而为新型抗癌药物的研发提供新靶点和新思路。

As a p53 target gene Killin, its promoter methylation is closely related to the occurrence of many cancers such as cowden syndrome, breast cancer and thyroid cancer. Killin tumor suppressor mechanism, more in-depth research has its high affinity binding and inhibition of DNA synthesis, and related to cell cycle S and G2 arrest. In recent years, Team found that Killin inhibits the occurrence of tumor closely related to its function in the G1 phase of the cell cycle. Killin is involved in p53-mediated arrest of G1 phase by up-regulating p21. However, the specific function and molecular mechanism of Killin in p53-mediated G1 phase arrest are unclear. Therefore, the project aims to carry out three aspects on the basis of the previous studies: 1) identification of Killin’s function in p53-mediated G1 arrest; 2) revealed the molecules of p53 → Killin → p21 → G1 arrest mechanism; 3）exploring the correlation between the expression of Killin and p21 in clinical colon cancer specimens and its relationship with malignancy. This study will elucidate the specific function and molecular mechanism of Killin in p53-mediated G1 arrest, which will provide new targets and new ideas for the development of new anticancer drugs.