肿瘤细胞迁移导致的死亡率在我国和世界范围内均居高不下。微丝细胞骨架是细胞实现运动的结构基础，其动态重组与肿瘤细胞的迁移密切联系，一直受到基础和临床领域的高度关注。肌球蛋白myosin-18B与微丝应力纤维共定位，其基因突变在多种癌症中被发现，但对其具体功能和分子机制的研究尚不深入。前期工作中，我们建立了细胞骨架的生物成像和生物力学研究方法和分析流程，提出myosin-18B在肿瘤细胞中促进微丝应力纤维融合与成熟的功能机制。本项目中，我们将综合运用细胞-生化-分子生物学手段、生物成像和生物力学的前沿技术，从发育进化、空间结构、信号转导、生物力学和互作网络五个方面全面探讨myosin-18B的调控机制。本项目将帮助我们深入了解肿瘤细胞中myosin-18B的致病机理、进一步认识由其调控的微丝应力纤维在肿瘤细胞迁移中的作用，促进我们发现myosin-18B基因异常疾病治疗的新途径和新靶点。

Tumor cell migration represents the most common cause of cancer-related death worldwide and in China. Actin cytoskeleton provides the structure basis for tumor cell to migrate, which drawing increasing attention in multiple research field. Myosin-18B, the mutations of which were found in various cancers, localizes in actin stress fibers. However, the physiological functions and molecular mechanisms of it have remained elusive. We have designed the experimental pipeline utilizing advanced techniques to examine the function of myosin-18B in actin stress fiber assembly. We propose to fully dissect the roles and mechanisms of myosin-18B from evolution and development, biophysics, signaling pathway, mechanical-sensing and interactome point of view, with the combination of molecular and cellular biology, bio-imaging and biomechanics methods. This project will increase our understanding of myosin-18B related disease and will shed new lights on its targeted therapy.