BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1812040001?filename=Model.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1812040001?filename=V2.cpsprimaryOK200Sarubini KananathanNon-curatedL2V4https://www.ebi.ac.uk/biomodels/MODEL181204000124345497falseBioModelsModelsSBMLBedessem2014 HiF 1 a mediated response to hypoxia on the G1/S transition2014MODEL1812040001B Bedessem, Angélique StéphanouB Bedessem24345497, Hypoxia is known to influence the cell cycle by increasing the G1 phase duration or by inducing a quiescent state (arrest of cell proliferation). This entry into quiescence is a mean for the cell to escape from hypoxia-induced apoptosis. It is suggested that some cancer cells have gain the advantage over normal cells to easily enter into quiescence when environmental conditions, such as oxygen pressure, are unfavorable [43,1]. This ability contributes in the appearance of highly resistant and aggressive tumor phenotypes [2]. The HiF-1α factor is the key actor of the intracellular hypoxia pathway. As tumor cells undergo chronic hypoxic conditions, HiF-1α is present in higher level in cancer than in normal cells. Besides, it was shown that genetic mutations promoting overstabilization of HiF-1α are a feature of various types of cancers [7]. Finally, it is suggested that the intracellular level of HiF-1α can be related to the aggressiveness of the tumors [53,24,4,10]. However, up to now, mathematical models describing the G1/S transition under hypoxia, did not take into account the HiF-1α factor in the hypoxia pathway. Therefore, we propose a mathematical model of the G1/S transition under hypoxia, which explicitly integrates the HiF-1α pathway. The model reproduces the slowing down of G1 phase under moderate hypoxia, and the entry into quiescence of proliferating cells under severe hypoxia. We show how the inhibition of cyclin D by HiF-1α can induce quiescence; this result provides a theoretical explanation to the experimental observations of Wen et al. (2010) [50]. Thus, our model confirms that hypoxia-induced chemoresistance can be linked, for a part, to the negative regulation of cyclin D by HiF-1α.. null, 248. UJF-Grenoble 1, CNRS, Laboratory TIMC-IMAG/DyCTIM, UMR 5525, 38041 Grenoble, France. Electronic address: Baptiste.Bedessem@imag.fr.skananathan@ebi.ac.ukEMBL-EBIHypoxia is known to influence the cell cycle by increasing the G1 phase duration or by inducing a quiescent state (arrest of cell proliferation). This entry into quiescence is a mean for the cell to escape from hypoxia-induced apoptosis. It is suggested that some cancer cells have gain the advantage over normal cells to easily enter into quiescence when environmental conditions, such as oxygen pressure, are unfavorable [43,1]. This ability contributes in the appearance of highly resistant and aggressive tumor phenotypes [2]. The HiF-1α factor is the key actor of the intracellular hypoxia pathway. As tumor cells undergo chronic hypoxic conditions, HiF-1α is present in higher level in cancer than in normal cells. Besides, it was shown that genetic mutations promoting overstabilization of HiF-1α are a feature of various types of cancers [7]. Finally, it is suggested that the intracellular level of HiF-1α can be related to the aggressiveness of the tumors [53,24,4,10]. However, up to now, mathematical models describing the G1/S transition under hypoxia, did not take into account the HiF-1α factor in the hypoxia pathway. Therefore, we propose a mathematical model of the G1/S transition under hypoxia, which explicitly integrates the HiF-1α pathway. The model reproduces the slowing down of G1 phase under moderate hypoxia, and the entry into quiescence of proliferating cells under severe hypoxia. We show how the inhibition of cyclin D by HiF-1α can induce quiescence; this result provides a theoretical explanation to the experimental observations of Wen et al. (2010) [50]. Thus, our model confirms that hypoxia-induced chemoresistance can be linked, for a part, to the negative regulation of cyclin D by HiF-1α.A mathematical model of HiF-1α-mediated response to hypoxia on the G1/S transition.Bedessem B B, Stéphanou A AfalseBedessem2014 - HiF-1 a -mediated response to hypoxia on the G1/S transitionNo description2018-12-042018-12-042018-12-04MODEL181204000124345497MODEL1812040001