RhoGDI2的磷酸化在SDF-1引起的β1整合素介导的Jurkat细胞迁移过程中的作用研究

骨髓微环境对白血病的发生和发展具有重要作用。骨髓内的SDF-1与表达于白血病细胞表面的CXCR4结合，促进白血病细胞向骨髓的侵润。此外，α4β1参与白血病细胞与骨髓基质的结合和细胞迁移，与白血病的愈后较差有关。有报道称，SDF-1很可能通过增加α4β1与骨髓基质的亲和力，增强白血病细胞对骨髓微环境巢亲和力，但具体机制有待研究。整合素的活化与受控于RhoGDI2的Rho的活性有关。RhoGDI2在实体瘤转移中的作用备受关注，但目前尚无RhoGDI2在白血病中的报道。我们的前期研究发现Jurkat细胞受SDF-1刺激后，RhoGDI2发生明显的磷酸化。本项目将通过体内和体外实验，研究RhoGDI2特异位点的磷酸化在SDF-1引起的Jurkat急性白血病细胞向骨髓基质侵润过程中的作用，阐明白血病细胞向骨髓侵润的关键信号通路，为治疗白血病提供理论依据和新的靶点。

The microenvironment in bone marrow is particularly important for the origination and development of leukemia. SDF-1 expressed by bone marrow binds to its receptor CXCR4 which is expressed in various leukemic cells. Their interaction directs the migration of leukemic cells into bone marrow. Additionally, α4β1 mediates binding of cells to marrow stromal elements and cellular migration, which is associated with the poor prognosis. It has been reported that SDF-1 increases the affinity of leukemia cells to the microenvironmental niches in the bone marrow, probably by increasing the affinity of α4β1 to bone matrix. However, this possibility and the specific mechanism has not yet been well studied.The activation of integrin is relevant to Rho which is tightly regulated by RhoGDI2. The role of RhoGDI2 in the migration and metastasis of solid tumor has been widely investigated. However, till now there's no report on its role in leukemia. In our previous experiment, we found obvious phosphorylation of RhoGDI2 in Jurkat cells treated with SDF-1. In this project, we will, via in vivo and in vitro experiments, investigate the effects of specific phosphorylation of RhoGDI2 on the migration of Jurkat cells to bone marrow which is induced by SDF-1, find out the crucial signal pathway in the migration of leukemic cells into bone marrow, and thereby provide theoretical refferences and novel targets for the cure of leukemia.