Pin1/YAP pathway mediates matrix stiffness-induced epithelial-mesenchymal transition driving cervical cancer metastasis via a non-Hippo mechanism

作者全名："Yang, Long; Li, Jingwen; Zang, Guangchao; Song, Sijie; Sun, Zhengwen; Li, Xinyue; Li, Yuanzhu; Xie, Zhenhong; Zhang, Guangyuan; Gui, Ni; Zhu, Shu; Chen, Tingting; Cai, Yikui; Zhao, Yinping"

作者地址："[Yang, Long; Li, Jingwen; Zang, Guangchao; Song, Sijie; Sun, Zhengwen; Li, Xinyue; Li, Yuanzhu; Xie, Zhenhong; Zhang, Guangyuan; Gui, Ni; Zhu, Shu; Chen, Tingting; Cai, Yikui; Zhao, Yinping] Chongqing Med Univ, Lab Teaching & Management Ctr, Lab Tissue & Cell Biol, 1 Med Coll Rd, Chongqing 400016, Peoples R China"

通信作者："Zhao, YP (通讯作者)，Chongqing Med Univ, Lab Teaching & Management Ctr, Lab Tissue & Cell Biol, 1 Med Coll Rd, Chongqing 400016, Peoples R China."

来源：BIOENGINEERING & TRANSLATIONAL MEDICINE

ESI学科分类：Multidisciplinary

WOS号：WOS:000821487500001

JCR分区：Q1

影响因子：7.4

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：epithelial-mesenchymal transition; extracellular matrix stiffness; PPIase non-mitotic a-interaction 1; yes-associated protein

摘要："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."

基金机构："Chongqing Municipal Education Commission Foundation [CY200405]; Lab Teaching & Management Center in Chongqing Medical University [LTMC202006]; National Natural Science Foundation of China [82100493]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0189]; Project of Science and Technology of Chongqing Yuzhong District [20200111]; Project of Tutorial System of Medical Undergraduate in Lab Teaching & Management Center in Chongqing Medical University [LTMCMTS201905, LTMCMTS202102]"

基金资助正文："Chongqing Municipal Education Commission Foundation, Grant/Award Number: CY200405; Lab Teaching & Management Center in Chongqing Medical University, Grant/Award Number: LTMC202006; National Natural Science Foundation of China, Grant/Award Number: 82100493; the Natural Science Foundation of Chongqing, Grant/Award Number: cstc2020jcyj-msxmX0189; the Project of Science and Technology of Chongqing Yuzhong District, Grant/Award Number: 20200111; the Project of Tutorial System of Medical Undergraduate in Lab Teaching & Management Center in Chongqing Medical University, Grant/Award Numbers: LTMCMTS201905, LTMCMTS202102"