Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation
Abstract Hyperthermic intraperitoneal chemotherapy’s role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46358-w |
| _version_ | 1827321393375608832 |
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| author | Xiaohang Yang Xingyuan Hu Jingjing Yin Wenting Li Yu Fu Bin Yang Junpeng Fan Funian Lu Tianyu Qin Xiaoyan Kang Xucui Zhuang Fuxia Li Rourou Xiao Tingyan Shi Kun Song Jing Li Gang Chen Chaoyang Sun |
| author_facet | Xiaohang Yang Xingyuan Hu Jingjing Yin Wenting Li Yu Fu Bin Yang Junpeng Fan Funian Lu Tianyu Qin Xiaoyan Kang Xucui Zhuang Fuxia Li Rourou Xiao Tingyan Shi Kun Song Jing Li Gang Chen Chaoyang Sun |
| author_sort | Xiaohang Yang |
| collection | DOAJ |
| description | Abstract Hyperthermic intraperitoneal chemotherapy’s role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer. |
| first_indexed | 2024-04-25T01:05:22Z |
| format | Article |
| id | doaj.art-de5d710211044ea2888fe1d839437ff2 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-25T01:05:22Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-de5d710211044ea2888fe1d839437ff22024-03-10T12:16:47ZengNature PortfolioNature Communications2041-17232024-03-0115112310.1038/s41467-024-46358-wComprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activationXiaohang Yang0Xingyuan Hu1Jingjing Yin2Wenting Li3Yu Fu4Bin Yang5Junpeng Fan6Funian Lu7Tianyu Qin8Xiaoyan Kang9Xucui Zhuang10Fuxia Li11Rourou Xiao12Tingyan Shi13Kun Song14Jing Li15Gang Chen16Chaoyang Sun17Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Shihezi University ShiheziDepartment of Gynecology and Obstetrics, Zhongnan Hospital of Wuhan UniversityOvarian Cancer Program, Department of Gynecologic Oncology, Zhongshan Hospital, Fudan UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityDepartment of Gynecologic Oncology, Sun Yat-sen Memorial HospitalCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyCancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Hyperthermic intraperitoneal chemotherapy’s role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer.https://doi.org/10.1038/s41467-024-46358-w |
| spellingShingle | Xiaohang Yang Xingyuan Hu Jingjing Yin Wenting Li Yu Fu Bin Yang Junpeng Fan Funian Lu Tianyu Qin Xiaoyan Kang Xucui Zhuang Fuxia Li Rourou Xiao Tingyan Shi Kun Song Jing Li Gang Chen Chaoyang Sun Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation Nature Communications |
| title | Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation |
| title_full | Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation |
| title_fullStr | Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation |
| title_full_unstemmed | Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation |
| title_short | Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation |
| title_sort | comprehensive multi omics analysis reveals wee1 as a synergistic lethal target with hyperthermia through cdk1 super activation |
| url | https://doi.org/10.1038/s41467-024-46358-w |
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