Role of aryl hydrocarbon receptor in cancer

Aryl hydrocarbon receptor (AHR), a cytosolic ligand-activated transcription factor, belongs to the member of bHLH/PAS family of heterodimeric transcriptional regulators and is widely expressed in a variety of animal species and humans. Recent animal and human data suggested that AHR is involved in various signaling pathways critical to cell normal homeostasis, which covers multiple aspects of physiology, such as cell proliferation and differentiation, gene regulation, cell motility and migration, inflammation and others. Dysregulation of these physiological processes is known to contribute to events such as tumor initiation, promotion, and progression. Increasing epidemiological and experimental animal data provided substantial support for an association between abnormal AHR function and cancer, implicating AHR may be a novel drug-interfering target for cancers. The proposed underlying mechanisms of its actions in cancer involved multiple aspects, (a) inhibiting the functional expression of the key anti-oncogenes (such as p53 and BRCA1), (b) promoting stem cells transforming and angiogenesis, (c) altering cell survival, proliferation and differentiation by influencing the physiologic processes of cell-cycle, apoptosis, cell contact-inhibition, metabolism and remodel of extracellular matrix, and cell–matrix interaction, (d) cross-talking with the signaling pathways of estrogen receptor and inflammation. This review aims to provide a brief overview of recent investigations into the role of AHR and the underlying mechanisms of its actions in cancer, which were explored by the new technologies emerging in recent years.