Cervical cancer metastasis is an important cause of death in cervical cancer. Previous studies have shown that epithelial–mesenchymal transition (EMT) of tumors promotes its invasive and metastatic capacity. Alterations in the extracellular matrix (ECM) and mechanical signaling are closely associated with cancer cell metastasis. However, it is unclear how matrix stiffness as an independent cue triggers EMT and promotes cervical cancer metastasis. Using collagen-coated polyacrylamide hydrogel models and animal models, we investigated the effect of matrix stiffness on EMT and metastasis in cervical cancer. Our data showed that high matrix stiffness promotes EMT and migration of cervical cancer hela cell lines in vitro and in vivo. Notably, we found that matrix stiffness regulates yes-associated protein (YAP) activity via PPIase non-mitotic a-interaction 1 (Pin1) with a non-Hippo mechanism. These data indicate that matrix stiffness of the tumor microenvironment positively regulates EMT in cervical cancer through the Pin1/YAP pathway, and this study deepens our understanding of cervical cancer biomechanics and may provide new ideas for the treatment of cervical cancer.

中文翻译：

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Pin1/YAP通路介导基质硬度诱导的上皮-间质转化，通过非Hippo机制驱动宫颈癌转移


宫颈癌转移是宫颈癌死亡的重要原因。既往研究表明肿瘤的上皮-间质转化（EMT）可促进其侵袭和转移能力。细胞外基质（ECM）和机械信号的改变与癌细胞转移密切相关。然而，目前尚不清楚基质硬度作为独立线索如何触发 EMT 并促进宫颈癌转移。利用胶原涂层聚丙烯酰胺水凝胶模型和动物模型，我们研究了基质硬度对宫颈癌 EMT 和转移的影响。我们的数据表明，高基质硬度可促进宫颈癌 Hela 细胞系在体外和体内的 EMT 和迁移。值得注意的是，我们发现基质硬度通过 PPIase 非有丝分裂 a 相互作用 1 (Pin1) 与非 Hippo 机制调节 yes 相关蛋白 (YAP) 活性。这些数据表明肿瘤微环境的基质刚度通过Pin1/YAP通路正向调节宫颈癌的EMT，本研究加深了我们对宫颈癌生物力学的认识，可能为宫颈癌的治疗提供新思路。