The extracellular matrix (ECM) exerts physiological activity, facilitates cell-to-cell communication, promotes cell proliferation and metastasis, and provides mechanical support for tumor cells. The development of solid tumors is often associated with increased stiffness. A stiff ECM promotes mechanotransduction, and the predominant transcription factors implicated in this phenomenon are YAP/TAZ, β-catenin, and NF-κB. In this study, we aimed to investigate whether YAP is a critical mediator linking matrix stiffness and PD-L1 in lung adenocarcinoma. We confirmed that YAP, PD-L1, and Ki-67, a marker of cell proliferation, increase as the matrix stiffness increases in vitro using the lung adenocarcinoma cell lines PC9 and HCC827 cells. The knockdown of YAP decreased the expression of PD-L1 and Ki-67, and conversely, the overexpression of YAP increased the expression of PD-L1 and K-67 in a stiff-matrix environment (20.0 kPa). Additionally, lung cancer cells were cultured in a 3D environment, which provides a more physiologically relevant setting, and compared to the results obtained from 2D culture. Similar to the findings in 2D culture, it was confirmed that YAP influenced the expression of PD-L1 and K-67 in the 3D culture experiment. Our results suggest that matrix stiffness controls PD-L1 expression via YAP activation, ultimately contributing to cell proliferation.
细胞外基质（ECM）具有生理活性，促进细胞间通讯、细胞增殖与转移，并为肿瘤细胞提供机械支撑。实体瘤的发展常伴随基质硬度增加。高硬度的ECM促进机械信号转导，其中涉及的主要转录因子包括YAP/TAZ、β-catenin和NF-κB。本研究旨在探讨YAP是否在肺腺癌中作为连接基质硬度与PD-L1表达的关键介质。通过体外实验，我们使用肺腺癌细胞系PC9和HCC827证实，随着基质硬度增加，YAP、PD-L1及细胞增殖标志物Ki-67的表达均上升。在硬度为20.0 kPa的基质环境中，敲低YAP可降低PD-L1和Ki-67的表达；反之，过表达YAP则增加PD-L1和Ki-67的表达。此外，研究将肺癌细胞置于更符合生理条件的3D环境中培养，并与2D培养结果进行比较。3D培养实验结果显示，与2D培养相似，YAP同样影响PD-L1和Ki-67的表达。我们的研究表明，基质硬度通过激活YAP调控PD-L1表达，最终促进细胞增殖。
肿瘤(癌症)患者之家