One of the hallmarks of cancer progression is strong drug resistance during clinical treatments. The tumor microenvironment is closely associated with multidrug resistance, the optimization of tumor microenvironments may have a strong therapeutic effect. In this study, we configured polyacrylamide hydrogels of varying stiffness [low (10 kPa), intermediate (38 kPa) and high (57 kPa)] to simulate tissue physical matrix stiffness across different stages of breast cancer. After treatment with doxorubicin, cell survival rates on intermediate stiffness substrate are significantly higher. We find that high expression of ILK and YAP reduces the survival rates of breast cancer patients. Drug resistance is closely associated with the inactivation of the hippo pathway protein Merlin/MST/LATS and the activation of YAP. These results not only highlight the understanding of drug resistance mechanisms but also serve as a new basis for developing breast cancer treatment delivery systems.

中文翻译：

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基质刚度调节ILK介导的YAP活化，以控制乳腺癌细胞的耐药性。

癌症进展的标志之一是在临床治疗过程中强烈的耐药性。肿瘤微环境与多药耐药性密切相关，优化肿瘤微环境可能具有很强的治疗作用。在这项研究中，我们配置了不同硬度[低（10 kPa），中（38 kPa）和高（57 kPa）]的聚丙烯酰胺水凝胶，以模拟乳腺癌不同阶段的组织物理基质刚度。用阿霉素治疗后，中等硬度基质上的细胞存活率明显更高。我们发现ILK和YAP的高表达降低了乳腺癌患者的生存率。耐药性与河马途径蛋白Merlin / MST / LATS的失活和YAP的激活密切相关。