力学微环境作为肿瘤微环境的一个重要物理特性备受关注，阐明力学微环境如何调控肿瘤恶性演进的力学生物学机制具有重要意义。我们前期研究发现小窝蛋白-1和YAP作为关键力学敏感分子，参与了肿瘤转移过程，与肿瘤恶性进程密切相关，但其力学调控机制和信号转导网络并不十分清楚。该项目聚焦肿瘤力学微环境中的基质刚度和受限空间等产生的应力如何影响肿瘤细胞恶性演进过程，并重点探讨其力学-生物学耦合机制和调控途径。采用生物力学分析、免疫共沉淀、流式细胞术及活细胞成像技术等分析手段，分别研究基质力学微环境对肿瘤细胞命运决定、细胞几何形态重构和细胞核形变、3D受限空间条件下肿瘤细胞趋化迁移、肿瘤干细胞“干性”维持和转移潜能等影响规律和分子调控机制，通过肿瘤动物模型进一步验证相关分子的功能。该项目对进一步深化认识肿瘤微环境力学特性的作用和肿瘤细胞恶性演进的力学生物学机制有重要指导意义，为肿瘤防治提供潜在的作用靶点。

As an important physical characteristic of tumor microenvironment, mechanical microenvironment has attracted much attention. It is of great significance to elucidate how mechanical microenvironment regulates tumor malignant evolutions. Previous studies have found that caveolin-1 and YAP, as key mechanically sensitive molecules, participate in the metastasis process of tumors and are closely related to the malignant process of tumors. However, their mechanisms of mechanical regulation and signal transduction networks are not very clear. This project focuses on how the matrix stiffness and the stress generated by the confined space in the micro-environment affect the malignant evolution of cancer cells, and analyses the mechanism of mechanical-biological coupling and the regulation pathway. Biomechanical analysis, immunoprecipitation, flow cytometry and living cell imaging techniques were used to study the effects of matrix mechanical microenvironment on the fate determination of cancer cells, cell geometry remodeling, nuclear deformation, chemotaxis and migration of cancer cells in three-dimensional confined space and the maintenance and metastasis potential of cancer stem cells. The function of related molecules was further validated by animal models. This project has important guiding significance for further understanding the role of the mechanical properties of tumor microenvironment and the biomechanical mechanism of tumor malignant evolutions, which provides potential targets for cancer prevention and treatment.