title: Antagonizing effects of membrane-acting androgens on the eicosanoid receptor OXER1 in prostate cancer.
abstract: 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.
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Kalyvianaki
authors.affiliation: Institute of Anatomy II, University Hospital Jena, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Gebhart
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Peroulis
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Panagiotopoulou
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: Fotini
authors.initials: F
authors.lastname: Kiagiadaki
authors.affiliation: Department of Pharmacology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.|Institute of Molecular Biology &Biotechnology, Foundation of Research &Technology-Hellas (IMBB-FORTH), Heraklion, Greece.
authors.forename: Iosif
authors.initials: I
authors.lastname: Pediaditakis
authors.affiliation: Proteomics Facility at Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology-Hellas, Heraklion, Crete.
authors.forename: Michalis
authors.initials: M
authors.lastname: Aivaliotis
authors.affiliation: Department of Pathology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Moustou
authors.affiliation: Department of Pathology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Tzardi
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, GR-71003, Greece.
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
mesh_terms: D000728:Androgens / Q000737:chemistry* / Q000235:genetics; D016718:Arachidonic Acid / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D062105:Molecular Docking Simulation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018055:Receptors, Eicosanoid / Q000737:chemistry* / Q000235:genetics; D013739:Testosterone / Q000737:chemistry / Q000235:genetics
chemical_list: D000728:Androgens; C504018:OXER1 protein, human; D018055:Receptors, Eicosanoid; D016718:Arachidonic Acid; D013739:Testosterone