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
Year: 2025
Type: article
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.
Source: Journal of Medical Virology
DOI: 10.1002/jmv.70422
Authors: Milica Velimirović, Alicia Avenhaus, Claudia Lohrey, Julia Bulkescher, Felix Hoppe‐Seyler, Karin Hoppe‐Seyler
Institutions: German Cancer Research Center, Heidelberg University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,730
OpenAlex ID: W4410900693