Background: Aryl hydrocarbon receptor (AhR) is an exogenous ligand-activating or constitutively active transcription factor. AhR regulates cellular differentiation, cell migration and other molecular and cellular processes. In general, AhR is biologically a very complex molecule in terms of its structure and functions in stemness, differentiation and clinical diseases. Here we review the debated issue of AhR in stem cell and cancer stem cell signaling.Methods: We searched literatures in PubMed and Google Scholar for related articles to review the AhR function and signal transduction in stem cells and cancer stem cells. Experimental data and results were analyzed. Results: It has been shown that AhR is an oncogenic protein but recent studies suggest that AhR can also inhibit cancer signaling through cancer stem cell pathways which are mostly common in OCT4. AhR either activates or inhibits tumorigenesis possibly through regulation of stemness or differentiation. Furthermore, how AhR can switch this function is largely unknown. Conclusion: AhR may inhibit or promote stem cell/cancer stem cell signaling through molecular switches of ageing, tissue specific signaling, ligand, and systems interaction networks. Targeting these signaling would provide a new avenue for efficient therapy in precision medicine.
Keywords: AhR, cancer, stem cell, OCT4, TCDD, molecular switch.