以紫杉类为基础的联合化疗方案一直是晚期或复发转移的宫颈鳞癌一线化疗方案，但目前缺乏预测该化疗方案适应性、有效性及预后的分子标志物。端粒及端粒酶结合蛋白PinX1被认为具有端粒酶抑制功能并调节肿瘤细胞端粒稳定，但其生物学功能尚未完全明确。我们前期研究发现，PinX1在宫颈鳞癌组织中高表达，并在体内外影响宫颈鳞癌细胞对紫杉醇的敏感性，其发挥作用的方式可能与纺锤体组装检查点有关。我们还发现PinX1与细胞骨架结合蛋白LIMA1存在相互结合作用，后者可能通过交叉连接的方式调节应力纤维张力并参与到微管的稳定，进而“开关”纺锤体组装检查点。故本课题拟从分子水平、细胞水平、动物模型、和临床病例四个方面系统分析阐述PinX1可作为筛选宫颈鳞癌细胞以紫杉醇为基础的化疗方案的分子靶标，并进一步研究其相关的作用机制，为肿瘤相关机制研究提供新的思路，为针对宫颈鳞癌的治疗及新一代抗肿瘤药物增敏提供一定的客观基础。

Clinically, combined chemotherapy based on paclitaxel is a main treatment for advanced human cervical squamous cell carcinomas (CSCC). However, it is deficient to identify reliable molecular characteristics in CSCC patients to determine who will benefit from the combination chemotherapy regimen. The telomere/telomerase binding factor PinX1 is an intrinsic telomerase inhibitor and contributes to telomere maintenance, but its other biological function still need to explore. Our previously studies demonstrated that PinX1 protein overexpressed in CSCC tissue and regulating CSCC cells response to paclitaxel. In this proposal, we will study the protein of PinX1 served as biomarker in sensitizing CSCC cells to paclitaxel at molecular level, cellular level, animal model level and clinical case analysis, respectively. In addition, we discovered that PinX1 protein interacted with cytoskeleton associated protein LIMA1, which regulates actin dynamics by crossing-linking and stabilizing filaments. We will further investigate the possible molecular mechanisms and biological function of the interaction between PinX1 and LIMA1. The role of PinX1-mediated paclitaxel sensitivity might provide new therapeutic strategy for improving the combination chemotherapy response of CSCC patients, and represent a new direction for the development of a new generation of microtubule drugs.