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| Home > Publications database > 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. |
| Home > Publications database > 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. |
| Journal Article | DKFZ-2025-01130 |
; ; ; ; ;
2025
Wiley
Bognor Regis [u.a.]
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Please use a persistent id in citations: doi:10.1002/jmv.70422
Abstract: 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.
Keyword(s): Humans (MeSH) ; Cellular Senescence (MeSH) ; Cell Line, Tumor (MeSH) ; Trans-Activators: genetics (MeSH) ; Trans-Activators: metabolism (MeSH) ; Cell Hypoxia (MeSH) ; Papillomaviridae (MeSH) ; Papillomavirus Infections (MeSH) ; Cell Cycle Proteins (MeSH) ; Proto-Oncogene Proteins c-myb (MeSH) ; A‐MYB ; B‐MYB ; cervical cancer ; human papillomavirus (HPV) ; hypoxia ; senescence ; Trans-Activators ; MYBL2 protein, human ; MYB protein, human ; Cell Cycle Proteins ; Proto-Oncogene Proteins c-myb
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