细胞骨架在肝细胞肝癌肿瘤微环境中的生物力学调控及其对靶向药物疗效的研究

肝细胞肝癌（HCC）的发病率和死亡率在我国和世界范围内均居高不下。HCC合并肝硬化十分普遍，而肝硬化这一特殊的肿瘤微环境与HCC发生发展的密切联系及其对HCC靶向药物疗效的干扰，一直受到基础和临床领域的高度关注。随着技术手段的进步，细胞骨架对生物力学的关键调控及微环境中物理因素对肿瘤发生发展的影响，正成为深入认识肿瘤的新突破点。我们建立了HCC的生物力学研究方法及细胞骨架分析流程,并在前期工作中发现HCC微环境中细胞骨架相关蛋白存在差异调控。我们将综合运用细胞-生化-分子生物学的手段、生物力学的前沿技术和临床转化的研究方法，重点探讨肿瘤微环境中生物力学因素对HCC发生、发展的影响，揭示其中细胞骨架相关的调控机理，探索改进肝细胞肝癌靶向药物疗效的新策略。本课题将帮助我们深入了解HCC的发生发展机理、进一步认识物理因素在肿瘤微环境中的作用，帮助我们开拓肝癌靶向药物研发的新思路。

Hepatocellular carcinoma (HCC) represents the most common cause of cancer-related death worldwide and in China. HCC almost exclusively arises in cirrhotic livers, which creates a tumor microenvironment antagonizing targeted therapies currently available. Understanding this tumor microenvironment is drawing increasing attention in multiple research fields. Cytoskeleton regulates cellular mechanics and participates in mechanotransduction in the tumor microenvironment. We found differential regulation of cytoskeletal proteins and associated factors in HCC microenvironment. We have designed the experimental pipeline utilizing advanced techniques in mechanical and cell biology to examine the roles and regulations of the cytoskeleton in HCC microenvironment. We propose to fully dissect the roles and mechanisms of microenvironmental tissue and cellular mechanics during HCC progression with the combination of molecular and cellular biology, biomechanics and translational medicine. This project will increase our understanding of HCC and will shed new lights on its targeted therapy.