CMTM是申请者在国际上首次报道的新基因家族，CMTM3是其成员之一，定位于抑癌基因富集区域16q22.1。CMTM3在原发性胃癌组织和胃癌来源的细胞系中表达下调或缺失，其启动子区存在甲基化修饰，CMTM3阳性表达患者的生存预后显著优于阴性表达者。在胃癌细胞系中恢复其表达，可以显著抑制细胞迁移和侵袭，降低ERK1/2的磷酸化，抑制MMP2的表达及活性。相关结果发表于Cancer Res、Cancer Sci。本项目将进一步研究CMTM3发挥功能的关键结构域；明确CMTM3的相互作用蛋白及其功能；通过shRNA和Cmtm3条件性敲除小鼠，研究其在胃癌发生中的作用机制。总之，本项目前期工作基础扎实，创新性强，延续性好。其顺利进行，有助于深入了解MARVEL结构域蛋白的功能和作用机制；促进胃癌的发病机制研究。

CMTM (CKLF-like MARVEL transmemberane domain-containing family) is a novel gene family reported by the applicant. CMTM3 is one member of the family. It is located at the tumor suppressor locus 16q22.1. CMTM3 was reduced or silenced by promoter methylation in primary gastric cancer tissues and cell lines. The prognosis of gastric cancer patients with CMTM3 expression was better than those without its expression. Restoration of CMTM3 significantly inhibited migration and invasion of gastric cancer cells and decreased the expression and activity of MMP2 and the phosphorylation of ERK1?2. The above results were published in Cancer Res, Cancer Sci. In this project, we will investigate the key functional domain of CMTM3, identify its interacting proteins and their function, and analyze its role in the development of gastric cancer using shRNA and Cmtm3 conditional knockout mice. In summary, this project is original and feasible with solid preliminary work, which will contribute to the function and mechanism of MARVEL domain containing proteins and the pathogenesis of gastric cancer.