Abstract
Aryl hydrocarbon receptor (AhR), an evolutionary conserved transcription factor, is a pleiotropic signal transductor. Thanks to its promiscuous ligand binding domain, during the evolution of eukaryotic cells its developmental functions were integrated with biosensor functions. Its activation by a multitude of endogenous and exogenous molecules stimulates its participation in several pathways, some of which are linked to inflammation and breast cancer (BC). Over time, the study of this malignancy has led to the identification of several therapeutic targets in cancer cells. An intense area of study is dedicated to BC phenotypes lacking adequate targets. In this context, due to its high constitutive activation in BC, AhR is currently gaining more and more attention. In this review, I have considered its interactions with: 1. the immune system, whose dysregulation is a renowned cancer hallmark; 2. interleukin 6 (IL6) which is a pivotal inflammatory marker and is closely correlated to breast cancer risk; 3. NF-kB, another evolutionary conserved transcription factor, which plays a key role in immunoregulatory functions, inflammatory response and breast carcinogenesis; 4. kynurenine, a tryptophan-derived ligand that activates and bridges AhR to chronic inflammation and breast carcinogenesis. Overall, the data here presented form an interesting framework where AhR is an interesting connector between inflammation and BC.
Highlights
Aryl hydrocarbon receptor (AhR), an environmentally sensitive transcription factor, is one of the more evolutionary conserved molecules in living cells
Considering the evolutionary conservation, it makes sense to hypothesize that over time, biosensor functions have been added to its physiological role, which to this day remains elusive
NC-xenobiotic responsive elements (XREs) and XRE have no sequence homology and interact with different proteins, this suggesting that AhR has different targets. They demonstrated that the complex AhR/Kruppel-like factor 6 (KLF6) is of pivotal importance in the control of cell cycle, as it regulates the expression of p21Cip1, or, cyclin-dependent kinase inhibitor 1A (CDKN1A), which inhibits the cell cycle and regulates cell metastasis by switching between invasion and proliferation [17]
Summary
AhR, an environmentally sensitive transcription factor, is one of the more evolutionary conserved molecules in living cells. NC-XRE and XRE have no sequence homology and interact with different proteins, this suggesting that AhR has different targets They demonstrated that the complex AhR/KLF6 is of pivotal importance in the control of cell cycle, as it regulates the expression of p21Cip, or, cyclin-dependent kinase inhibitor 1A (CDKN1A), which inhibits the cell cycle and regulates cell metastasis by switching between invasion and proliferation [17]. Considering these data, it is reasonable to hypothesize that originally AhR had a checkpoint role in the cellular metabolism and that, over time, AhR has acquired the ability to bind to a multitude of molecules, both exogenous and endogenous. All three strains of AhR knockout mice are affected by hepatic and vascular defects, but only one strain shows immune system abnormalities represented by T cells deficiency in their spleens [43]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
