Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway
Abstract Deoxyhypusine synthase (DHPS) is an enzyme encoded by the DHPS gene, with high expression in various cancers, including ovarian cancer (OC). DHPS regulates the translation initiation factor EIF5A, and EIF5A2 knockout inhibits OC tumor growth and metastasis by blocking the epithelial-to-mese...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-85466-5 |
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| author | Guannan Zhao Xinxin Zhao Ziping Liu Baojin Wang Peixin Dong Hidemichi Watari Lawrence M. Pfeffer Gabor Tigyi Wenjing Zhang Junming Yue |
| author_facet | Guannan Zhao Xinxin Zhao Ziping Liu Baojin Wang Peixin Dong Hidemichi Watari Lawrence M. Pfeffer Gabor Tigyi Wenjing Zhang Junming Yue |
| author_sort | Guannan Zhao |
| collection | DOAJ |
| description | Abstract Deoxyhypusine synthase (DHPS) is an enzyme encoded by the DHPS gene, with high expression in various cancers, including ovarian cancer (OC). DHPS regulates the translation initiation factor EIF5A, and EIF5A2 knockout inhibits OC tumor growth and metastasis by blocking the epithelial-to-mesenchymal transition (EMT) and the TGFβ pathway. In this study, we show that DHPS is amplified in OC patients, and its elevated expression correlates with poor survival. Using lentiviral CRISPR/Cas9 vectors for DHPS knockout, we observed EMT inhibition in SKOV3 and OVCAR8 cells through suppressed hypusination and reduced EIF5A2 expression. Inhibition of DHPS activity with GC7 similarly blocked hypusination and EMT. Disrupting DHPS expression, either genetically or pharmacologically, inhibited primary tumor growth and metastasis in OC mouse models. These findings suggest that targeting DHPS and inhibiting hypusination could be promising strategies for OC treatment. |
| format | Article |
| id | doaj-art-634d7fdb74f2462eba6faae982e0e51e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-634d7fdb74f2462eba6faae982e0e51e2025-01-12T12:22:18ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-85466-5Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathwayGuannan Zhao0Xinxin Zhao1Ziping Liu2Baojin Wang3Peixin Dong4Hidemichi Watari5Lawrence M. Pfeffer6Gabor Tigyi7Wenjing Zhang8Junming Yue9Department of Pathology and Laboratory Medicine, Collage of Medicine, the University of Tennessee Health Science CenterDepartment of Obstetrics and Gynecology, The Third Hospital of Zhengzhou UniversityDepartment of Obstetrics and Gynecology, The Third Hospital of Zhengzhou UniversityDepartment of Obstetrics and Gynecology, The Third Hospital of Zhengzhou UniversityDepartment of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido UniversityDepartment of Obstetrics and Gynecology, Hokkaido University School of Medicine, Hokkaido UniversityDepartment of Pathology and Laboratory Medicine, Collage of Medicine, the University of Tennessee Health Science CenterDepartment of Physiology, Collage of Medicine, the University of Tennessee Health Science CenterDepartment of Genetics, Genomics & Informatics, Collage of Medicine, University of Tennessee Health Science CenterDepartment of Pathology and Laboratory Medicine, Collage of Medicine, the University of Tennessee Health Science CenterAbstract Deoxyhypusine synthase (DHPS) is an enzyme encoded by the DHPS gene, with high expression in various cancers, including ovarian cancer (OC). DHPS regulates the translation initiation factor EIF5A, and EIF5A2 knockout inhibits OC tumor growth and metastasis by blocking the epithelial-to-mesenchymal transition (EMT) and the TGFβ pathway. In this study, we show that DHPS is amplified in OC patients, and its elevated expression correlates with poor survival. Using lentiviral CRISPR/Cas9 vectors for DHPS knockout, we observed EMT inhibition in SKOV3 and OVCAR8 cells through suppressed hypusination and reduced EIF5A2 expression. Inhibition of DHPS activity with GC7 similarly blocked hypusination and EMT. Disrupting DHPS expression, either genetically or pharmacologically, inhibited primary tumor growth and metastasis in OC mouse models. These findings suggest that targeting DHPS and inhibiting hypusination could be promising strategies for OC treatment.https://doi.org/10.1038/s41598-025-85466-5DHPSEIF5AOvarian cancerEMTMetastasisTGFβ |
| spellingShingle | Guannan Zhao Xinxin Zhao Ziping Liu Baojin Wang Peixin Dong Hidemichi Watari Lawrence M. Pfeffer Gabor Tigyi Wenjing Zhang Junming Yue Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway Scientific Reports DHPS EIF5A Ovarian cancer EMT Metastasis TGFβ |
| title | Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway |
| title_full | Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway |
| title_fullStr | Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway |
| title_full_unstemmed | Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway |
| title_short | Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway |
| title_sort | knockout or inhibition of dhps suppresses ovarian tumor growth and metastasis by attenuating the tgfβ pathway |
| topic | DHPS EIF5A Ovarian cancer EMT Metastasis TGFβ |
| url | https://doi.org/10.1038/s41598-025-85466-5 |
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