Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer
Abstract Sirtuin 7 (SIRT7), a member of the sirtuin family of NAD+-dependent deacetylases, plays a vital role in cancer, exhibiting context-dependent functions across various malignancies. Our study investigates the role of SIRT7 depletion in head and neck squamous cell carcinoma (HNSCC) progression...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-83349-9 |
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| author | Marta Halasa Syeda Afshan Anna Wawruszak Agata Borkowska Klaudia Brodaczewska Alicja Przybyszewska-Podstawka Joanna Kalafut Marzena Baran Adolfo Rivero-Müller Andrzej Stepulak Matthias Nees |
| author_facet | Marta Halasa Syeda Afshan Anna Wawruszak Agata Borkowska Klaudia Brodaczewska Alicja Przybyszewska-Podstawka Joanna Kalafut Marzena Baran Adolfo Rivero-Müller Andrzej Stepulak Matthias Nees |
| author_sort | Marta Halasa |
| collection | DOAJ |
| description | Abstract Sirtuin 7 (SIRT7), a member of the sirtuin family of NAD+-dependent deacetylases, plays a vital role in cancer, exhibiting context-dependent functions across various malignancies. Our study investigates the role of SIRT7 depletion in head and neck squamous cell carcinoma (HNSCC) progression. In vitro and 3D organotypic models demonstrated that SIRT7 knock-out attenuates cancer cell viability, proliferation, and motility as well as induces downregulation of migration- and epithelial-mesenchymal transition (EMT)-related gene expression. Moreover, the SIRT7 loss results in slower organoid formation and less invasive organoid morphology, validated by vimentin downregulation. The SIRT7 loss potentiates S-phase arrest in cell cycle progression after 5-FU treatment and elevates the ratio of dead cells. Additionally, SIRT7 deletion reduces the expression of G1 phase-associated proteins, Cyclin D and CDK4. Altogether, our study highlights SIRT7 as a promising therapeutic target in HNSCC, enhancing the effectiveness of treatment modalities such as combinational treatment. |
| format | Article |
| id | doaj-art-eaf353586d7d453192e0ab5a3a250e52 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-eaf353586d7d453192e0ab5a3a250e522025-01-19T12:20:39ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-83349-9Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancerMarta Halasa0Syeda Afshan1Anna Wawruszak2Agata Borkowska3Klaudia Brodaczewska4Alicja Przybyszewska-Podstawka5Joanna Kalafut6Marzena Baran7Adolfo Rivero-Müller8Andrzej Stepulak9Matthias Nees10Department of Biochemistry and Molecular Biology, Medical University of LublinFICAN West Cancer Centre, Institute of Biomedicine, University of TurkuDepartment of Biochemistry and Molecular Biology, Medical University of LublinLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, National Research InstituteLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, National Research InstituteDepartment of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinDepartment of Biochemistry and Molecular Biology, Medical University of LublinAbstract Sirtuin 7 (SIRT7), a member of the sirtuin family of NAD+-dependent deacetylases, plays a vital role in cancer, exhibiting context-dependent functions across various malignancies. Our study investigates the role of SIRT7 depletion in head and neck squamous cell carcinoma (HNSCC) progression. In vitro and 3D organotypic models demonstrated that SIRT7 knock-out attenuates cancer cell viability, proliferation, and motility as well as induces downregulation of migration- and epithelial-mesenchymal transition (EMT)-related gene expression. Moreover, the SIRT7 loss results in slower organoid formation and less invasive organoid morphology, validated by vimentin downregulation. The SIRT7 loss potentiates S-phase arrest in cell cycle progression after 5-FU treatment and elevates the ratio of dead cells. Additionally, SIRT7 deletion reduces the expression of G1 phase-associated proteins, Cyclin D and CDK4. Altogether, our study highlights SIRT7 as a promising therapeutic target in HNSCC, enhancing the effectiveness of treatment modalities such as combinational treatment.https://doi.org/10.1038/s41598-024-83349-9HNSCCSIRT75-FUcell cycleHDAC |
| spellingShingle | Marta Halasa Syeda Afshan Anna Wawruszak Agata Borkowska Klaudia Brodaczewska Alicja Przybyszewska-Podstawka Joanna Kalafut Marzena Baran Adolfo Rivero-Müller Andrzej Stepulak Matthias Nees Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer Scientific Reports HNSCC SIRT7 5-FU cell cycle HDAC |
| title | Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer |
| title_full | Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer |
| title_fullStr | Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer |
| title_full_unstemmed | Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer |
| title_short | Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer |
| title_sort | loss of sirtuin 7 impairs cell motility and proliferation and enhances s phase cell arrest after 5 fluorouracil treatment in head and neck cancer |
| topic | HNSCC SIRT7 5-FU cell cycle HDAC |
| url | https://doi.org/10.1038/s41598-024-83349-9 |
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