{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOXER1 is a G‐protein–coupled receptor that binds the arachidonic acid metabolite 5‑oxo‑ETE, mediating diverse cell signaling events. Initial studies revealed that this receptor is widely expressed in various tissues—with notable intensity in immune cells—and is potently activated by 5‑oxo‑ETE as well as related polyunsaturated fatty acids, resulting in Gαi‐dependent inhibition of cAMP production and other downstream effects. These findings established an important role for OXER1 in inflammatory signaling and mediator responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer cells—notably in prostate cancer—OXER1 expression is elevated and critically supports cell survival. Blockade of this receptor in prostate cancer models reduces viability by interfering with anti‐apoptotic signaling cascades that involve phospholipase C–β and PKCε, underscoring its key role in survival pathways. In parallel, studies in steroidogenic cells have demonstrated that overexpression of OXER1 enhances cAMP‐dependent progesterone production and amplifies StAR protein induction through ERK1/2 activation. Moreover, recent evidence indicates that OXER1 also functions as a membrane androgen receptor; testosterone binding to OXER1 can antagonize the actions of its natural ligand, thereby modulating rapid intracellular signaling events—such as calcium mobilization—and influencing processes like cell migration and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in survival and steroidogenesis, OXER1 is a critical mediator of cell migration and chemoattraction. Activation of OXER1 triggers rearrangements in the actin cytoskeleton, integrin activation, and calcium fluxes that are essential for leukocyte chemotaxis and for cancer cell motility during wound‐healing–like processes. These signaling events, which can be parsed out by employing biased antagonists that preferentially block Gβγ‐mediated pathways, highlight OXER1 as a promising therapeutic target in inflammatory diseases and cancer metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takeshi Hosoi, Yutaka Koguchi, Emiko Sugikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel human eicosanoid receptor coupled to G(i/o)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M203194200"}], "href": "https://doi.org/10.1074/jbc.M203194200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12065583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12065583"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carol E Jones, Suzanne Holden, Laurent Tenaillon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.63.3.471"}], "href": "https://doi.org/10.1124/mol.63.3.471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12606753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12606753"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lin Lin, Fei Dai, Jinjin Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biological Roles of 5-Oxo-6,8,11,14-Eicosatetraenoic Acid and the OXE Receptor in Allergic Diseases: Collegium Internationale Allergologicum Update 2024."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Arch Allergy Immunol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000535560"}], "href": "https://doi.org/10.1159/000535560"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38176394"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38176394"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sathish Sundaram, Jagadananda Ghosh "}, {"type": "b", "children": [{"type": "t", "text": "Expression of 5-oxoETE receptor in prostate cancer cells: critical role in survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.10.189"}], "href": "https://doi.org/10.1016/j.bbrc.2005.10.189"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16289380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16289380"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sivalokanathan Sarveswaran, Jagadananda Ghosh "}, {"type": "b", "children": [{"type": "t", "text": "OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2013.04.027"}], "href": "https://doi.org/10.1016/j.canlet.2013.04.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23643940"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23643940"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Melina Dattilo, Isabel Neuman, Mariana Muñoz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OxeR1 regulates angiotensin II and cAMP-stimulated steroid production in human H295R adrenocortical cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2015.01.040"}], "href": "https://doi.org/10.1016/j.mce.2015.01.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25657046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25657046"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Konstantina Kalyvianaki, Veronika Gebhart, Nikolaos Peroulis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antagonizing effects of membrane-acting androgens on the eicosanoid receptor OXER1 in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep44418"}], "href": "https://doi.org/10.1038/srep44418"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28290516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28290516"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Konstantina Kalyvianaki, Athanasios A Panagiotopoulos, Panagiotis Malamos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Membrane androgen receptors (OXER1, GPRC6A AND ZIP9) in prostate and breast cancer: A comparative study of their expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Steroids (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.steroids.2019.01.006"}], "href": "https://doi.org/10.1016/j.steroids.2019.01.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30707908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30707908"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Athanasios A Panagiotopoulos, Konstantina Kalyvianaki, Bourcin Serifoglou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OXER1 mediates testosterone-induced calcium responses in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2021.111487"}], "href": "https://doi.org/10.1016/j.mce.2021.111487"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34634385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34634385"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Viktoria Konya, Stefanie Blättermann, Katharina Jandl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A biased non-Gαi OXE-R antagonist demonstrates that Gαi protein subunit is not directly involved in neutrophil, eosinophil, and monocyte activation by 5-oxo-ETE."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1302013"}], "href": "https://doi.org/10.4049/jimmunol.1302013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24733850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24733850"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Konstantina Kalyvianaki, Irene Drosou, George Notas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced OXER1 expression is indispensable for human cancer cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2021.11.024"}], "href": "https://doi.org/10.1016/j.bbrc.2021.11.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34775286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34775286"}]}]}]}