Unveiling the mechanistic role of the Aryl hydrocarbon receptor in environmentally induced Breast cancer

The aryl hydrocarbon receptor (AhR) is a crucial cytosolic evolutionary conserved ligand-activated transcription factor and a pleiotropic signal transducer. The biosensor activity of the AhR is attributed to the promiscuity of its ligand-binding domain. Evidence suggests exposure to environmental toxins such as polycyclic aromatic hydrocarbons, polychlorinated biphenyls and halogenated aromatic hydrocarbons activates the AhR signaling pathway. The constitutive activation of the receptor signaling system leads to multiple health adversities and enhances the risk of several cancers, including breast cancer (BC). This review evaluates several mechanisms that integrate the tumor-inducing property of such environmental contaminants with the AhR pathway assisting in BC tumorigenesis, progress and metastasis. Intriguingly, immune evasion is identified as a prominent hallmark in BC. Several emerging pieces of evidence have identified AhR as a potent immunosuppressive effector in several cancers. Through AhR signaling pathways, some tumors can avoid immune detection. Thus the relevance of AhR in the immunomodulation of breast tumors and its putative mode of action in the breast tumor microenvironment are discussed in this review. Additionally, the work also explores BC stemness and its associated inflammation in response to several environmental cues. The review elucidates the context-dependent ambiguous behavior of AhR either as an oncogene or a tumor suppressor with respect to its ligand. Conclusively, this holistic piece of literature attempts to potentiate AhR as a promising pharmacological target in BC and updates on the therapeutic manipulation of its various exogenous and endogenous ligands.