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primary topic: Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB

Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB
type: Article
abstract: Hypoxia is a hallmark of solid tumors, including HPV-positive cervical cancers, and it poses a significant challenge to cancer treatment, as hypoxic tumor regions are often associated with increased therapy resistance and poor patient prognosis. One possible contributing factor to this resistance is the ability of hypoxic cancer cells to evade cellular senescence – a process leading to an irreversible growth arrest. While the repression of the HPV E6/E7 oncogenes in normoxic HPV-positive cells efficiently induces senescence, hypoxic HPV-positive cells, despite efficiently shutting off E6/E7 expression, evade senescence and induce a reversible growth arrest that can be overcome by reoxygenation. The overall aim of this thesis was to uncover mechanisms that enable hypoxic HPV-positive cancer cells to evade senescence. Through comparative gene and protein expression analyses following E6/E7 repression under normoxic and hypoxic conditions, I identified distinct regulatory patterns of key cell cycle regulatory factors. Notably, B-MYB emerged as a critical factor differentially regulated under these conditions. Its strong downregulation in normoxic cells following E6/E7 knockdown was associated with the onset of senescence, while its sustained expression under hypoxia correlated with senescence evasion, suggesting a role for B-MYB in controlling this process. To further investigate the functional role of B-MYB, I performed knockdown experiments and assessed the phenotypic consequences using various cellular assays. Interestingly, B-MYB depletion led to a partial senescence induction under normoxia. I further showed that this limited senescence response was due to the compensatory induction of a B-MYB paralog, A-MYB, which could counteract the pro-senescent effects of B-MYB loss. Consequently, the combined repression of both B-MYB and A-MYB was needed for efficient senescence induction under normoxia. Strikingly, I found that this compensatory mechanism is disrupted under…
date: 2025
author list: authors
type: EPrint
type: DoctoralThesisEPrint
is part of: repository
has document: Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (PDF)
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subject: 570 Biowissenschaften, Biologie

Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (PDF)
type: Document
has file: Thesis Milica Velimirovic.pdf
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Milica Velimirovic
type: Person
given name: Milica
family name: Velimirovic

Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (Other)
type: Document
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Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (Other)
type: Document
is version of: Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (PDF)
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Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (Other)
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Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (Other)
type: Document
is version of: Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (PDF)
is volatile version of: Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (PDF)
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Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (Other)
type: Document
is version of: Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (PDF)
is volatile version of: Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB (PDF)
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primary topic: Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB

570 Biowissenschaften, Biologie
type: Concept
preferred label: 570 Life sciences @en