Constitutive Aryl Hydrocarbon Receptor Signaling in Prostate Cancer Progression.

Abstract

Research on the aryl hydrocarbon receptor (AhR) has largely focused on its activation by various environmental toxins. Consequently, only limited inferences have been made regarding its constitutive activity in the absence of an exogenous ligands. Evidence has shown that AhR is constitutively active in advanced prostate cancer cell lines which model castration resistant prostate cancer (CRPC). CRPC cells can thrive in an androgen depleted environment. However, AR signaling still plays a major role. Although several mechanisms have been suggested for the sustained AR signaling, much is still unknown. Recent studies suggest that crosstalk between constitutive AhR and Src kinase may sustained AR signaling in CRPC. AhR forms a protein complex with Src and plays a role in regulating Src activity. Several groups have reported that tyrosine phosphorylation of AR protein by Src leads to AR activation, thereby promoting the development of CRPC. This review evaluates reports that implicate constitutive AhR as a key regulator of AR signaling in CRPC by utilizing Src as a signaling intermediate.