The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal response
Abstract The platinum-based compounds are widely used in treating various types of cancer through their heavy metal component platinum. However, the development of chemoresistance often limits their clinical effectiveness. In this study, we report the roles of heavy metal response and its associated...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-13661-8 |
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| author | Hui Chen Yue Xu Dingshan Chen Di Xiao Bing Yang Wenqi Wang Han Han |
| author_facet | Hui Chen Yue Xu Dingshan Chen Di Xiao Bing Yang Wenqi Wang Han Han |
| author_sort | Hui Chen |
| collection | DOAJ |
| description | Abstract The platinum-based compounds are widely used in treating various types of cancer through their heavy metal component platinum. However, the development of chemoresistance often limits their clinical effectiveness. In this study, we report the roles of heavy metal response and its associated Hippo pathway in regulating platinum-based chemotherapy. Our data show that the MTF1-dependent heavy metal response induces cancer cell resistance to platinum-based compounds both in vitro and in vivo. This resistance is mitigated by Hippo pathway-mediated phosphorylation of MTF1. Moreover, pharmacological activation of the Hippo pathway sensitizes cancer cells to platinum-based compounds. Clinically, lung adenocarcinoma (LUAD) patients with high MTF1 activity exhibit poor overall survival rates, and Hippo pathway inactivation is positively correlated with elevated MTF1 transcriptional activity in platinum-treated LUAD patients. Collectively, our findings not only unveil a critical role of the Hippo-MTF1 pathway in regulating the response to platinum-based chemotherapy, but also suggest new strategies to enhance its efficacy by targeting the heavy metal response. |
| format | Article |
| id | doaj-art-69a5f456e1fb41e4b72e742018d5f044 |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-69a5f456e1fb41e4b72e742018d5f0442025-02-09T12:41:44ZengBMCBMC Cancer1471-24072025-02-0125111110.1186/s12885-025-13661-8The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal responseHui Chen0Yue Xu1Dingshan Chen2Di Xiao3Bing Yang4Wenqi Wang5Han Han6Department of Pathophysiology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School (School of Basic Medical Sciences), Wuhan UniversityDepartment of Pathophysiology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School (School of Basic Medical Sciences), Wuhan UniversityDepartment of Pathophysiology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School (School of Basic Medical Sciences), Wuhan UniversityDepartment of Pathophysiology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School (School of Basic Medical Sciences), Wuhan UniversityDepartment of Developmental and Cell Biology, University of CaliforniaDepartment of Developmental and Cell Biology, University of CaliforniaDepartment of Pathophysiology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School (School of Basic Medical Sciences), Wuhan UniversityAbstract The platinum-based compounds are widely used in treating various types of cancer through their heavy metal component platinum. However, the development of chemoresistance often limits their clinical effectiveness. In this study, we report the roles of heavy metal response and its associated Hippo pathway in regulating platinum-based chemotherapy. Our data show that the MTF1-dependent heavy metal response induces cancer cell resistance to platinum-based compounds both in vitro and in vivo. This resistance is mitigated by Hippo pathway-mediated phosphorylation of MTF1. Moreover, pharmacological activation of the Hippo pathway sensitizes cancer cells to platinum-based compounds. Clinically, lung adenocarcinoma (LUAD) patients with high MTF1 activity exhibit poor overall survival rates, and Hippo pathway inactivation is positively correlated with elevated MTF1 transcriptional activity in platinum-treated LUAD patients. Collectively, our findings not only unveil a critical role of the Hippo-MTF1 pathway in regulating the response to platinum-based chemotherapy, but also suggest new strategies to enhance its efficacy by targeting the heavy metal response.https://doi.org/10.1186/s12885-025-13661-8PlatinumChemotherapyCisplatinHippo pathwayMTF1 |
| spellingShingle | Hui Chen Yue Xu Dingshan Chen Di Xiao Bing Yang Wenqi Wang Han Han The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal response BMC Cancer Platinum Chemotherapy Cisplatin Hippo pathway MTF1 |
| title | The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal response |
| title_full | The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal response |
| title_fullStr | The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal response |
| title_full_unstemmed | The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal response |
| title_short | The Hippo pathway promotes platinum-based chemotherapy by inhibiting MTF1-dependent heavy metal response |
| title_sort | hippo pathway promotes platinum based chemotherapy by inhibiting mtf1 dependent heavy metal response |
| topic | Platinum Chemotherapy Cisplatin Hippo pathway MTF1 |
| url | https://doi.org/10.1186/s12885-025-13661-8 |
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