How the AHR became important in cancer: The role of chronically active AHR in cancer aggression
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PROVIDER: PRJNA687764 | ENA |
REPOSITORIES: ENA
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Project description:Sometimes biological research is an act of faith, a belief that untangling complex biologic interactions on a very basic level in-and-of itself eventually leads to larger and broader implications for human health. Indeed, sometimes focusing on the trees leads to a better view of the forest. This has been the case for the aryl hydrocarbon receptor (AHR). For decades, the AHR was studied for its role in environmental chemical toxicity i.e., as a quirk of nature and a mediator of unintended consequences of human pollution. During that period, it was not certain that the AHR had a “normal” physiological function. However, the ongoing accumulation of data from an ever-expanding variety of studies on cancer, cancer immunity, autoimmunity, organ development, and other areas bears witness to a staggering array of AHR-controlled normal and pathological activities. The objective of this review is to discuss how the AHR has gone from a likely contributor to genotoxic environmental carcinogen-induced cancer to a master regulator of malignant cell progression and cancer aggression. Particular focus was placed on the association between AHR activity and poor outcomes, feedback loops that control chronic AHR activity in cancer, and the role of chronically active AHR in driving cancer cell invasion, migration, cancer stem cell characteristics, and survival.
2023-12-11 | GSE163859 | GEO
Project description:For decades, the aryl hydrocarbon receptor (AHR) was studied for its role in environmental chemical toxicity i.e., as a quirk of nature and a mediator of unintended consequences of human pollution. During that period, it was not certain that the AHR had a "normal" physiological function. However, the ongoing accumulation of data from an ever-expanding variety of studies on cancer, cancer immunity, autoimmunity, organ development, and other areas bears witness to a staggering array of AHR-controlled normal and pathological activities. The objective of this review is to discuss how the AHR has gone from a likely contributor to genotoxic environmental carcinogen-induced cancer to a master regulator of malignant cell progression and cancer aggression. Particular focus is placed on the association between AHR activity and poor cancer outcomes, feedback loops that control chronic AHR activity in cancer, and the role of chronically active AHR in driving cancer cell invasion, migration, cancer stem cell characteristics, and survival.
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Project description:The AhR is a ligand activated transcription factor that may be important in normal skin physiology. We compared gene expression profiles between AhR Wt and AhR KO primary mouse keratinocyte cultures. We identified 391 genes that were differentially expressed with a 1.5 fold cutoff and p<.05, and identified the AhR as an important regulator of genes involved in normal epidermal differentiation. AhR Wt primary keratinocyte cultures (n=4) were compared with AhR KO primary keratinocyte cultures (n=3)
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Project description:AHR regulated genes in Colorectal Cancer
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Project description:The AhR is a ligand activated transcription factor that may be important in normal skin physiology. We compared gene expression profiles between AhR Wt and AhR KO primary mouse keratinocyte cultures. We identified 391 genes that were differentially expressed with a 1.5 fold cutoff and p<.05, and identified the AhR as an important regulator of genes involved in normal epidermal differentiation.
2015-07-01 | GSE62490 | GEO
Project description: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.
2022-05-31 | PXD028992 | Pride
Project description:Macrophages that acquire an immunosuppressive phenotype are crucial for creating the pre-metastatic niche (PMN), which is essential for facilitating breast cancer metastasis to the distant organ. Our study showed that increased aryl hydrocarbon receptor (AHR) activity in lung macrophages is vital for establishing the immunosuppressive PMN in breast cancer. AHR activation led to higher PD-L1 expression on macrophages through directly binding to the promoter of Pdl1, subsequently, promoting Treg cell differentiation in the PMN. Mice with Ahr conditional deletion in macrophages had reduced lung metastasis of breast cancer. The elevated AHR level in PMN macrophages was induced by GM-CSF released from breast cancer cells, which activated STAT5 and prevented AHR ubiquitination in macrophages. In breast cancer patients, the expression of AHR and PD-L1 correlated with Treg cell infiltration, and high AHR expression was associated with a poor prognosis. Our findings uncover a previously unknown cellular and molecular mechanism through which macrophages establish the lung PMN in breast cancer.
2024-10-18 | GSE277589 | GEO
Project description:Modulation of action choices according to the environmental context is crucial for animal survival and reproductive success1. Aggression, despite its general importance as a social behavior2, can become detrimental if uncontrolled3,4. However, the genetic and neural basis for aggression control through active suppression remains largely unknown. Here we found nvy, a Drosophila homolog of vertebrate myeloid translocation gene (MTG)5 involved in transcriptional regulation6-8, suppresses aggression through a specific subset of neurons. Mutation of the nvy gene resulted in hyper-aggressiveness, which was rescued by neuronal expression of human MTGs as well as Drosophila nvy. The mutant exhibited persistent aggression under various contexts in which wild-type flies switch their behavioral patterns. Knockdown of nvy in octopaminergic/tyraminergic (OA/TA) neurons increased aggression, phenocopying the nvy deletion. Cell-type specific transcriptomics on OA/TA neurons derived from the nvy mutants revealed aggression-controlling genes that are likely downstream of nvy. Moreover, we found that the nvy-expressing OA/TA neuronal subpopulations specifically suppress aggression. Our results presents a powerful genetic model to unravel not only the neuronal systems that modulate aggression in a social context-dependent manner, but also the conserved molecular mechanism underlying the tumorigenesis caused by the MTG mutations.
2022-06-22 | GSE148630 | GEO
Project description:Genes relevant to manifestion of and variation in aggression behavior might be differentially expressed in lines selected for divergent levels of aggression. Keywords: selection group
2006-08-30 | GSE5404 | GEO