放疗在食管鳞癌的综合治疗中占据核心地位，但辐射抗拒仍旧是限制放疗疗效的瓶颈。我们前期研究表明PinX1通过调控端粒酶的端粒募集维持端粒稳定并介导了食管鳞癌对放疗的抵抗，但机制不清。我们通过质谱筛选并鉴定出PinX1新的相互作用蛋白RBM10。RBM10可以定位于Cajal小体，端粒酶的Cajal小体定位是其移动到端粒的关键步骤。这些提示PinX1与RBM10相互作用可能通过参与端粒酶运输的调控来影响肿瘤细胞的端粒稳定，从而调节其放疗敏感性。基于这些重要发现，本立项将从分子、细胞、动物及组织水平探讨PinX1和RBM10相互作用对肿瘤细胞端粒稳定及放疗敏感性的影响及调控机制，研究将揭示PinX1/RBM10 影响食管鳞癌细胞放疗疗效的分子机制并丰富端粒酶/端粒的调控通路，为食管鳞癌病人的治疗提供新靶点、新思路。

Radiotherapy has been widely used to treat esophageal squamous cell carcinoma (ESCC) patients in clinic. However, the mechanism by which ESCC responds or resist to radiotherapy remains unknown. Our preliminary results demonstrated that PinX1 induced cell resistance to RT through a new pathway of telomerase maintaining the telomere stability. We screened PinX1-interacting factors by mass spectrum and identified a new protein RBM10 (RNA binding motif protein 10). In addition, we found RBM10 could localize in Cajal body. It’s known that telomerase localizing in Cajal body is a critical step for telomerase achieving to telomere. These data indicated that PinX1/RBM10 may involve in telomerase transportation and regulate the therapeutic response of ESCC cells to radiation. However, the interaction mechanisms between PinX1 and RBM10 are still unclear. Therefore, based on these preliminary data, in this project we will investigate the impact of PinX1/RBM10 interactions on ESCC cells’ telomere stability and response to radiotherapy in vitro and in vivo. The success of this project will reveal the molecular mechanism by which PinX1/RBM10 interaction influences the ESCC cells’ therapeutic response to radiation. This study also will provide new supplementary information about the pathways of telomere maintenance. The study will bring about novel ideas and targets to optimize treatment strategies for ESCC patients in clinical settings.