Calumein分选途径与生理功能关系的分析

Calumenin (calu)属于CREC家族,人体中已报道有calu-1和calu-2两个异形体。我们发现了13个新calu异形体（calu-3-15），实验结果显示它们具有不同的亚细胞定位。在本项目中，我们将确定13个新异形体的细胞定位和功能，特别分析calu1/2通过不同的分选途径对细胞内膜系统的结构和功能的调控作用。第二，研究分泌到胞外的calu-1/2与细胞迁移和肿瘤转移等的关系。通过寻找calu-1/2在胞外和细胞膜上的相互作用蛋白，分析与calu-1/2及细胞迁移相关的细胞信号通路，阐明其抑制细胞迁移的分子机制。第三，应用过表达、RNA干涉及小鼠模型验等手段分析calu-1/2与肿瘤恶性化程度及转移的关系。通过大量临床肿瘤组织和癌旁组织的比较，探讨将其作为肿瘤恶性化程度指标的可能性。确定calu抑制肿瘤细胞转移的最小功能结构域，为寻找抑制肿瘤细胞转移药物提供新思路。

Calumenin (Calu), a CREC protein family member, contains two isoforms (calu-1 and calu-2) in human. We have newly identified thirteen calumenin isoforms (calu-3-15) with different subcellular localizations. In this project, we would like to investigate the precise intracellular localizations and functions of calu-3-15, and focus on the regulatory roles of calu-1/2 on the structure and function of endomembrane system through their sorting pathways. Moreover, we plan to study the extracellular function of calu-1/2, and their relationship with cell migration and tumor metastasis.To elucidate the molecular mechanism of calu-1/2 inhibiting cell migration, we will screen extracellular or membrane associating proteins, and analyze calu-1/2 related cell signaling pathways. Meanwhile, we will determin the relationship between calu-1/2 and tumor metastasis and malignancy by means of overexpression, RNAi and mouse model, as well as tumour sample comparison, which would facilitate the evaluation of calu-1/2 as a biomarker of tomour malignancy diagnosis.We also expect to determin the minimum functional domain of calu-1/2, and provide new clues for the development of anti-cancer drug.