Hypoxic HPV-positive cancer cells are particularly sensitive to the pro-senescent effects of B-MYB repression due to the lack of compensatory A-MYB induction
Tumor hypoxia is typically linked to increased therapy resistance and poor prognosis of many malignancies, including HPV-positive cancers. One possible resistance mechanism is the increased resistance of hypoxic tumor cells to cellular senescence. It is thus highly interesting to identify strategies...
Gespeichert in:
| Hauptverfasser: | , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
June 2025
|
| In: |
Journal of medical virology
Year: 2025, Jahrgang: 97, Heft: 6, Pages: 1-14 |
| ISSN: | 1096-9071 |
| DOI: | 10.1002/jmv.70422 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/jmv.70422 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.70422 
|
| Verfasserangaben: | Milica Velimirović, Alicia Avenhaus, Claudia Lohrey, Julia Bulkescher, Felix Hoppe-Seyler, Karin Hoppe-Seyler |
| Zusammenfassung: | Tumor hypoxia is typically linked to increased therapy resistance and poor prognosis of many malignancies, including HPV-positive cancers. One possible resistance mechanism is the increased resistance of hypoxic tumor cells to cellular senescence. It is thus highly interesting to identify strategies which could increase their pro-senescent susceptibility. In comparative analyses of normoxic and hypoxic HPV-positive cancer cells, we here uncover that the interconnection between B-MYB and its paralog A-MYB plays a key role for their senescence response, but shows a differential regulation under normoxia and hypoxia. In specific, we demonstrate that the pro-senescent response to B-MYB loss is counteracted by a compensatory upregulation of A-MYB under normoxia. Therefore, efficient induction of senescence in normoxic cells requires the downregulation of both B-MYB and A-MYB. Interestingly, this compensatory A-MYB induction is absent under hypoxia, rendering hypoxic cancer cells particularly sensitive to the pro-senescent effect of B-MYB repression. We further show that these regulatory effects are not confined to HPV-positive cancer cells, indicating that they could be broadly conserved between different cancer types. Collectively, our findings reveal that hypoxic cancer cells are particularly sensitive to B-MYB inhibition, which could provide a new strategy to target this therapeutically challenging cancer cell population. |
|---|---|
| Beschreibung: | Zuerst veröffentlicht: 30. Mai 2025 Gesehen am 12.09.2025 |
| Beschreibung: | Online Resource |
| ISSN: | 1096-9071 |
| DOI: | 10.1002/jmv.70422 |