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@ARTICLE{Velimirovic:301746,
      author       = {M. Velimirovic$^*$ and A. Avenhaus$^*$ and C. Lohrey$^*$
                      and J. Bulkescher$^*$ and F. Hoppe-Seyler$^*$ and K.
                      Hoppe-Seyler$^*$},
      title        = {{H}ypoxic {HPV}-{P}ositive {C}ancer {C}ells {A}re
                      {P}articularly {S}ensitive to the {P}ro-{S}enescent
                      {E}ffects of {B}-{MYB} {R}epression {D}ue to the {L}ack of
                      {C}ompensatory {A}-{MYB} {I}nduction.},
      journal      = {Journal of medical virology},
      volume       = {97},
      number       = {6},
      issn         = {0146-6615},
      address      = {Bognor Regis [u.a.]},
      publisher    = {Wiley},
      reportid     = {DKFZ-2025-01130},
      pages        = {e70422},
      year         = {2025},
      note         = {#EA:D365#LA:D365#},
      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.},
      keywords     = {Humans / Cellular Senescence / Cell Line, Tumor /
                      Trans-Activators: genetics / Trans-Activators: metabolism /
                      Cell Hypoxia / Papillomaviridae / Papillomavirus Infections
                      / Cell Cycle Proteins / Proto-Oncogene Proteins c-myb /
                      A‐MYB (Other) / B‐MYB (Other) / cervical cancer (Other)
                      / human papillomavirus (HPV) (Other) / hypoxia (Other) /
                      senescence (Other) / Trans-Activators (NLM Chemicals) /
                      MYBL2 protein, human (NLM Chemicals) / MYB protein, human
                      (NLM Chemicals) / Cell Cycle Proteins (NLM Chemicals) /
                      Proto-Oncogene Proteins c-myb (NLM Chemicals)},
      cin          = {D365},
      ddc          = {610},
      cid          = {I:(DE-He78)D365-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40444458},
      pmc          = {pmc:PMC12123558},
      doi          = {10.1002/jmv.70422},
      url          = {https://inrepo02.dkfz.de/record/301746},
}