Accumulating evidence during the last decades revealed that
androgen can exert membrane initiated actions that involve signaling via specific
kinases and the modulation of significant cellular processes, important for
prostate cancer cell growth and
metastasis. Results of the present work clearly show that
androgens can specifically act at the membrane level via the GPCR oxoeicosanoid receptor 1 (OXER1) in
prostate cancer cells. In fact, OXER1 expression parallels that of membrane
androgen binding in
prostate cancer cell lines and
tumor specimens, while in silico docking simulation of OXER1 showed that
testosterone could bind to OXER1 within the same grove as
5-OxoETE, the natural
ligand of OXER1. Interestingly,
testosterone antagonizes the effects of
5-oxoETE on specific signaling pathways and rapid effects such as actin cytoskeleton reorganization that ultimately can modulate cell migration and
metastasis. These findings verify that membrane-acting
androgens exert specific effects through an antagonistic interaction with OXER1. Additionally, this interaction between
androgen and OXER1, which is an
arachidonic acid metabolite receptor expressed in
prostate cancer, provides a novel link between
steroid and
lipid actions and renders OXER1 as new player in the disease. These findings should be taken into account in the design of novel therapeutic approaches in
prostate cancer.