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Status: Bibliographieeintrag

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Verfasst von:Heber, Nora [VerfasserIn]   i
 Kuhn, Bianca [VerfasserIn]   i
 Strobel, Tobias [VerfasserIn]   i
 Lohrey, Claudia [VerfasserIn]   i
 Krijgsveld, Jeroen [VerfasserIn]   i
 Hoppe-Seyler, Karin [VerfasserIn]   i
 Hoppe-Seyler, Felix [VerfasserIn]   i
Titel:The impact of cycling hypoxia on the phenotype of HPV-positive cervical cancer cells
Verf.angabe:Nora Heber, Bianca J. Kuhn, Tobias D. Strobel, Claudia Lohrey, Jeroen Krijgsveld, Karin Hoppe-Seyler, Felix Hoppe-Seyler
E-Jahr:2023
Jahr:06 December 2023
Umfang:16 S.
Fussnoten:Gesehen am 28.03.2024
Titel Quelle:Enthalten in: Journal of medical virology
Ort Quelle:Bognor Regis [u.a.] : Wiley, 1977
Jahr Quelle:2023
Band/Heft Quelle:95(2023), 12, Artikel-ID e29280, Seite 1-16
ISSN Quelle:1096-9071
Abstract:Cycling hypoxia (cycH) is a prevalent form of tumor hypoxia that is characterized by exposure of tumor cells to recurrent phases of hypoxia and reoxygenation. CycH has been associated with a particularly aggressive cellular phenotype of tumor cells and increased therapy resistance. By performing comparative analyses under normoxia, physoxia, chronic hypoxia, and cycH, we here uncover distinct effects of cycH on the phenotype of human papillomavirus (HPV)-positive cervical cancer cells. We show that—other than under chronic hypoxia—viral E6/E7 oncogene expression is largely maintained under cycH as is the E6/E7-dependent regulation of p53 and retinoblastoma protein. Further, cycH enables HPV-positive cancer cells to evade prosenescent chemotherapy, similar to chronic hypoxia. Moreover, cells under cycH exhibit a particularly pronounced resistance to the proapoptotic effects of Cisplatin. Quantitative proteome analyses reveal that cycH induces a unique proteomic signature in cervical cancer cells, which includes a significant downregulation of luminal lysosomal proteins. These encompass the potentially proapoptotic cathepsins B and cathepsin L, which, however, appear not to affect the response to Cisplatin under any of the O2 conditions tested. Rather, we show that the proapoptotic Caspase 8/BH3-interacting domain death agonist (BID) cascade plays a pivotal role for the efficiency of Cisplatin-induced apoptosis in HPV-positive cancer cells under all investigated O2 conditions. In addition, we provide evidence that BID activation by Cisplatin is impaired under cycH, which could contribute to the high resistance to the proapoptotic effects of Cisplatin. Collectively, this study provides the first insights into the profound phenotypic alterations induced by cycH in HPV-positive cancer cells, with implications for their therapeutic susceptibility.
DOI:doi:10.1002/jmv.29280
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1002/jmv.29280
 Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.29280
 DOI: https://doi.org/10.1002/jmv.29280
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:BH3-interacting domain death agonist
 cervical cancer
 chemoresistance
 cisplatin (CDDP)
 human papillomavirus
 hypoxia
K10plus-PPN:1884571743
Verknüpfungen:→ Zeitschrift

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