Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells
Obstructive sleep apnea (OSA) affects a significant proportion of the population and is linked to increased rates of cancer development and a worse cancer outcome. OSA is characterized by nocturnal intermittent hypoxia and animal models of OSA-like intermittent hypoxia show increased tumor growth an...
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doaj-2fe1bacb76a042ecade04449324746982020-11-24T23:14:18ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-01-0120244510.3390/ijms20020445ijms20020445Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma CellsChloe-Anne Martinez0Bernadette Kerr1Charley Jin2Peter A. Cistulli3Kristina M. Cook4Charles Perkins Centre, Faculty of Medicine and Health, Northern Clinical School, The University of Sydney, Sydney NSW 2006, AustraliaCharles Perkins Centre, Faculty of Medicine and Health, Northern Clinical School, The University of Sydney, Sydney NSW 2006, AustraliaCharles Perkins Centre, Faculty of Medicine and Health, Northern Clinical School, The University of Sydney, Sydney NSW 2006, AustraliaCharles Perkins Centre, Faculty of Medicine and Health, Northern Clinical School, The University of Sydney, Sydney NSW 2006, AustraliaCharles Perkins Centre, Faculty of Medicine and Health, Northern Clinical School, The University of Sydney, Sydney NSW 2006, AustraliaObstructive sleep apnea (OSA) affects a significant proportion of the population and is linked to increased rates of cancer development and a worse cancer outcome. OSA is characterized by nocturnal intermittent hypoxia and animal models of OSA-like intermittent hypoxia show increased tumor growth and metastasis. Advanced tumors typically have regions of chronic hypoxia, activating the transcription factor, HIF-1, which controls the expression of genes involved in cancer progression. Rapid intermittent hypoxia from OSA has been proposed to increase HIF-1 activity and this may occur in tumors. The effect of exposing a developing tumor to OSA-like intermittent hypoxia is largely unknown. We have built a cell-based model of physiological OSA tissue oxygenation in order to study the effects of intermittent hypoxia in HCT116 colorectal cancer cells. We found that HIF-1α increases following intermittent hypoxia and that the expression of HIF-target genes increases, including those involved in glycolysis, the hypoxic pathway and extracellular matrix remodeling. Expression of these genes acts as a ‘hypoxic’ signature which is associated with a worse prognosis. The total dose of hypoxia determined the magnitude of change in the hypoxic signature rather than the frequency or duration of hypoxia-reoxygenation cycles per se. Finally, transcription of <i>HIF1A</i> mRNA differs in response to chronic and intermittent hypoxia suggesting that HIF-1α may be regulated at the transcriptional level in intermittent hypoxia and not just by the post-translational oxygen-dependent degradation pathway seen in chronic hypoxia.https://www.mdpi.com/1422-0067/20/2/445intermittent hypoxiaobstructive sleep apneaHIF-1cancerhypoxia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chloe-Anne Martinez Bernadette Kerr Charley Jin Peter A. Cistulli Kristina M. Cook |
spellingShingle |
Chloe-Anne Martinez Bernadette Kerr Charley Jin Peter A. Cistulli Kristina M. Cook Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells International Journal of Molecular Sciences intermittent hypoxia obstructive sleep apnea HIF-1 cancer hypoxia |
author_facet |
Chloe-Anne Martinez Bernadette Kerr Charley Jin Peter A. Cistulli Kristina M. Cook |
author_sort |
Chloe-Anne Martinez |
title |
Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells |
title_short |
Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells |
title_full |
Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells |
title_fullStr |
Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells |
title_full_unstemmed |
Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells |
title_sort |
obstructive sleep apnea activates hif-1 in a hypoxia dose-dependent manner in hct116 colorectal carcinoma cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-01-01 |
description |
Obstructive sleep apnea (OSA) affects a significant proportion of the population and is linked to increased rates of cancer development and a worse cancer outcome. OSA is characterized by nocturnal intermittent hypoxia and animal models of OSA-like intermittent hypoxia show increased tumor growth and metastasis. Advanced tumors typically have regions of chronic hypoxia, activating the transcription factor, HIF-1, which controls the expression of genes involved in cancer progression. Rapid intermittent hypoxia from OSA has been proposed to increase HIF-1 activity and this may occur in tumors. The effect of exposing a developing tumor to OSA-like intermittent hypoxia is largely unknown. We have built a cell-based model of physiological OSA tissue oxygenation in order to study the effects of intermittent hypoxia in HCT116 colorectal cancer cells. We found that HIF-1α increases following intermittent hypoxia and that the expression of HIF-target genes increases, including those involved in glycolysis, the hypoxic pathway and extracellular matrix remodeling. Expression of these genes acts as a ‘hypoxic’ signature which is associated with a worse prognosis. The total dose of hypoxia determined the magnitude of change in the hypoxic signature rather than the frequency or duration of hypoxia-reoxygenation cycles per se. Finally, transcription of <i>HIF1A</i> mRNA differs in response to chronic and intermittent hypoxia suggesting that HIF-1α may be regulated at the transcriptional level in intermittent hypoxia and not just by the post-translational oxygen-dependent degradation pathway seen in chronic hypoxia. |
topic |
intermittent hypoxia obstructive sleep apnea HIF-1 cancer hypoxia |
url |
https://www.mdpi.com/1422-0067/20/2/445 |
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