The complex biology of aryl hydrocarbon receptor activation in cancer and beyond

The aryl hydrocarbon receptor (AHR) signaling pathway is a complex regulatory network that plays a critical role in various biological processes, including cellular metabolism, development, and immune responses. The complexity of AHR signaling arises from multiple factors, including the diverse ligands that activate the receptor, the expression level of AHR itself, and its interaction with the AHR nuclear translocator (ARNT). Additionally, the AHR crosstalks with the AHR repressor (AHRR) or other transcription factors and signaling pathways and it can also mediate non-genomic effects. Finally, posttranslational modifications of the AHR and its interaction partners, epigenetic regulation of AHR and its target genes, as well as AHR-mediated induction of enzymes that degrade AHR-activating ligands may contribute to the context-specificity of AHR activation. Understanding the complexity of AHR signaling is crucial for deciphering its physiological and pathological roles and developing therapeutic strategies targeting this pathway. Ongoing research continues to unravel the intricacies of AHR signaling, shedding light on the regulatory mechanisms controlling its diverse functions.