CMTM是本室2003年在国际上首次报道的基因家族，其成员调控膜分子的转运和稳定性，CMTM3是其中之一。在已结题国自然基金资助下，我们证明CMTM3定位于细胞质膜和早期内体，通过增强Rab5活性调控EGFR的稳定性。数据库提示CMTM3的表达水平与利妥昔单抗的反应性成正相关。利妥昔单抗是抗CD20嵌合抗体，广泛用于治疗B细胞肿瘤和自身免疫病，总体反应率约50%，耐药现象严重。膜表面CD20的表达水平决定细胞对抗体的反应性，但CD20的表达调控机制有待研究。预实验表明CMTM3能稳定CD20，提高利妥昔单抗的反应性。我们推测，CMTM3可能通过促进CD20从早期内体进入循环内体、细胞质膜，抑制其泛素化，提高其稳定性。本项目将深入研究CMTM3稳定CD20的机制，分析其表达水平与利妥昔单抗治疗反应性的关系。其实施将为治疗相关疾病提供潜在分子标志物，有助于筛选获益人群，提高精准治疗效率。

CMTM is a gene family first reported by our laboratory in 2003. Its members can regulate the traffic and stability of membrane molecules. Funded by National Natural Science Foundation of China, we have demonstrated that CMTM3, one of its members, localizes at the plasma membrane as well as early endosomes, and regulates the stability of EGFR by enhancing Rab5 activity. Database analysis suggests that the expression level of CMTM3 is positively correlated to the response to Rituximab. Rituximab is a chimeric antibody against CD20, which is widely used in the treatment of B cell tumors and autoimmune diseases. Still, its overall response rate is about 50%, and the problem of drug resistance is serious. It has known that the expression level of CD20 on the membrane surface determines the response to Rituximab, but the regulation mechanism of CD20 expression needs further study. Our primary experiments have shown that CMTM3 can stabilize CD20 and increase the response to Rituximab. Therefore, we hypothesize that CMTM3 may enhance the stability of CD20 by promoting its traffic from early endosomes into the recycle endosome and cytoplasmic membrane, and inhibiting its ubiquitination. This project will further study the mechanism of how CMTM3 stabilizes CD20, and analyze relationship between the expression level of CMTM3 and the efficacy of Rituximab treatment. Its implementation will provide a potential molecular marker for related diseases, help to screen the benefit population, and ultimately improve the efficiency of precision treatment.