Hexokinase 2 is a transcriptional target and a positive modulator of AHR signalling
Abstract The aryl hydrocarbon receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanisti...
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Published in | Nucleic acids research Vol. 50; no. 10; pp. 5545 - 5564 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
10.06.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract
The aryl hydrocarbon receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood. We show that hexokinase 2 (HK2) a metabolic enzyme fuelling cancer cell growth, is a transcriptional target of AHR as well as a modulator of its activity. Expression of HK2 is positively regulated by AHR upon exposure to agonists both in human cells and in mice lung tissues. Conversely, over-expression of HK2 regulates the abundance of many proteins involved in the regulation of AHR signalling and these changes are linked with altered AHR expression levels and transcriptional activity. HK2 expression also shows a negative correlation with AHR promoter methylation in tumours, and these tumours with high HK2 expression and low AHR methylation are associated with a worse overall survival in patients. In sum, our study provides novel insights into how AHR signalling is regulated which may help our understanding of the context-specific effects of this pathway and may have implications in cancer. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC9178003 |
ISSN: | 0305-1048 1362-4962 |
DOI: | 10.1093/nar/gkac360 |