Rab34介导的囊泡运输对EMT转分化及其对细胞迁移、侵袭能力的调控作用和机制

囊泡运输是细胞最基本的生命活动之一，近年来发现囊泡运输与肿瘤的发生关系密切，而小分子GTP酶Rab蛋白在其中可能扮演重要角色。Rab34是一个重要的囊泡运输调控因子，参与细胞的分泌、内吞等，我们在前期的研究中发现，Rab34在高侵袭性乳腺癌细胞中显著高表达，而在正常乳腺细胞和低侵袭性乳腺癌细胞中表达极低；过表达Rab34促进细胞迁移；而且，Rab34活性异常会影响某些EMT标志物的表达水平。研究结果暗示，Rab34可能与EMT转分化相关，并由此调控细胞迁移、侵袭等过程。在本课题中，我们将利用分子生物学、细胞生物学、生物化学以及动物模型等技术手段，深入研究Rab34介导的囊泡运输对EMT标志蛋白的定位、运输、分选、降解的调控作用，以及这些调控作用对细胞迁移、肿瘤细胞侵袭、肿瘤发生及相关信号通路的影响，揭示Rab34通过调节EMT，从而调控细胞迁移、肿瘤细胞侵袭和肿瘤发生的新机制。

Membrane trafficking is one of the most foundmental cellular events, recent findings revealed that membrane trafficking is closely related to cancer, and the small GTPase Rab protein may play an important role in this relationship.Rab34 is a key regulator in membrane trafficking,including exocytosis and endocytosis. In our primary results, we found that Rab34 is highly expressed in high aggressive breast cancer cells, while the expression level is very low in normal cells or lower aggressive breast cancer cells; Over-expression of Rab34 can promote cell migration; In addition, abnormal activity of Rab34 affects the expression level of some EMT markers. The results suggest that Rab34 may regulate cell migration and cell invasion through modulating EMT. In this project, we will apply the technologies of molecular biology,cell biology,biochemistry and animal model to investigate the effects and regulation of Rab34-mediated membrane trafficking on the localization, transport, sorting and degradation of EMT markers, and the mechanisms for Rab34-mediated membrane trafficking in regulating cell migration, cell invasion and tumorigenesis.