染色体不稳定性或异常分离被广泛认为是癌症发生的标志性事件。食管癌作为一种高致死疾病，其发生发展是一个涉及多因素、多阶段、多基因变异累及相互作用的复杂过程，但具体分子调控机制并不清楚。我们前期工作证实在诸多肿瘤组织中高突变的动点蛋白SKAP被在食管癌中高表达的蛋白激酶GSK-3β磷酸化，位点为其Ser232/237位和Thr294位。磷酸化的SKAP与Kif2b协同参与有丝分裂纺锤体稳定性调控和染色体分离，预实验表明CLASP-1可能协同磷酸化SKAP参与调控其动点定位及动点微管连接。我们推测，被GSK-3β磷酸化的SKAP可能参与食管癌细胞有丝分裂调控，从而在食管癌发生发展中发挥作用。本课题将以磷酸化SKAP为切入点，探究其与协同作用蛋白Kif2b、CLASP-1在食管癌细胞周期中的时空动态性调节机制和生物学功能以及在食管癌发生发展中的临床意义，为治疗食管癌的新医疗手段奠定坚实的理论基础。

Loss or gain of whole chromosome, the form of chromosome instability commonly associated with cancers is thought to arise from aberrant chromosome segregation during cell division. As a highly lethal disease, the development of esophageal cancer is a complicated process involving various factors, multiple stages and multiple gene variation. However, the underlying molecular mechanisms remain undetermined. Previously, we have shown that protein kinase GSK-3β which is highly expressed in esophageal cancer can phosphorylate kinetochore protein SKAP at Ser232/237 and Thr294. We reason that phosphorylated SKAP by GSK-3β ensures is important to mitotic spindle dynamics and chromosome segregation cooperated with Kif2b. Our pre-experiments show that phosphorylated SKAP may also be involved in its kinetchore localization and constitute a dynamic link between spindle microtubule plus-ends and kinetchore cooperated with CLASP-1. We speculate that SKAP, which is phosphorylated by GSK-3β, may play a role in the development of esophageal cancer by participating in the regulation of mitosis. Taken together, in this proposal, we plan to further explore the spatiotemporal dynamic regulation mechanism and biological function of phosphorylated SKAP and synergistic protein Kif2b and CLASP in the cell cycle of esophageal cancer, and the clinical significance in the development of esophageal cancer.