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- W3095992502 abstract "Abstract Tumors experience temporal and spatial fluctuations in oxygenation. Hypoxia inducible transcription factors (HIF-α) in tumor cells are stabilized in response to low levels of oxygen and induce angiogenesis to re-supply oxygen. HIF-α stabilization is typically facultative, induced by hypoxia and reduced by normoxia. In some cancers, however, HIF-α stabilization becomes constitutive even under normoxia, a condition known as pseudohypoxia . Herein, we develop a mathematical model that predicts the effects of fluctuating levels of oxygen availability on stabilization of HIF-α and its client proteins based on fitness. The model shows that facultative regulation of HIF-α always promotes greater cell fitness than constitutive regulation. However, cell fitness is nearly identical regardless of HIF-α regulation strategy when there are rapid periodic fluctuations in oxygenation. Furthermore, the model predicts that stochastic changes in oxygenation favor facultative HIF-α regulation. We conclude that rapid and regular cycling of oxygenation levels selects for pseudohypoxia." @default.
- W3095992502 created "2020-11-09" @default.
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- W3095992502 date "2020-10-28" @default.
- W3095992502 modified "2023-09-23" @default.
- W3095992502 title "Cycling hypoxia selects for constitutive HIF stabilization" @default.
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- W3095992502 doi "https://doi.org/10.1101/2020.10.28.359018" @default.
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