title: A calixpyrrole derivative acts as an antagonist to GPER, a G-protein coupled receptor: mechanisms and models.
abstract: Estrogens regulate numerous pathophysiological processes, mainly by binding to and activating estrogen receptor (ER)α and ERβ. Increasing amounts of evidence have recently demonstrated that G-protein coupled receptor 30 (GPR30; also known as GPER) is also involved in diverse biological responses to estrogens both in normal and cancer cells. The classical ER and GPER share several features, including the ability to bind to identical compounds; nevertheless, some ligands exhibit opposed activity through these receptors. It is worth noting that, owing to the availability of selective agonists and antagonists of GPER for research, certain differential roles elicited by GPER compared with ER have been identified. Here, we provide evidence on the molecular mechanisms through which a calixpyrrole derivative acts as a GPER antagonist in different model systems, such as breast tumor cells and cancer-associated fibroblasts (CAFs) obtained from breast cancer patients. Our data might open new perspectives toward the development of a further class of selective GPER ligands in order to better dissect the role exerted by this receptor in different pathophysiological conditions. Moreover, calixpyrrole derivatives could be considered in future anticancer strategies targeting GPER in cancer cells.
authors.affiliation: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende 87036, Italy.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Lappano
authors.affiliation: U.O.S. Biopolymers and Proteomics, IST-National Institute for Cancer Research, Genova 16132, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Rosano
authors.affiliation: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende 87036, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Pisano
authors.affiliation: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende 87036, Italy.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Santolla
authors.affiliation: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende 87036, Italy.
authors.forename: Ernestina Marianna
authors.initials: EM
authors.lastname: De Francesco
authors.affiliation: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende 87036, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: De Marco
authors.affiliation: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende 87036, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Dolce
authors.affiliation: U.O.S. Biopolymers and Proteomics, IST-National Institute for Cancer Research, Genova 16132, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ponassi
authors.affiliation: U.O.S. Biopolymers and Proteomics, IST-National Institute for Cancer Research, Genova 16132, Italy.
authors.forename: Lamberto
authors.initials: L
authors.lastname: Felli
authors.affiliation: Department of Chemical Sciences, University of Messina, Messina 98166, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Cafeo
authors.affiliation: Department of Chemical Sciences, University of Messina, Messina 98166, Italy.
authors.forename: Franz Heinrich
authors.initials: FH
authors.lastname: Kohnke
authors.affiliation: Breast Cancer Unit, Regional Hospital, Cosenza 87100, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abonante
authors.affiliation: Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende 87036, Italy marcello.maggiolini@unical.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
mesh_terms: D000818:Animals; D001681:Biological Assay; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D009369:Neoplasms / Q000473:pathology; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014981:Xenopus
chemical_list: D008024:Ligands; D011758:Pyrroles; D043562:Receptors, G-Protein-Coupled
keywords: Breast cancer; Calixpyrroles; Cancer-associated fibroblasts; Estrogen; GPR30/GPER; Signal transduction