A calixpyrrole derivative acts as an antagonist to GPER, a G-protein coupled receptor: mechanisms and models

Disease Models & Mechanisms

Sergio Abonante¹  Grazia Cafeo²  Franz Heinrich Kohnke²  Assunta Pisano³  Ernestina Marianna De Francesco³  Rosamaria Lappano³  Paola De Marco³  Marcello Maggiolini³  Maria Francesca Santolla³  Vincenza Dolce³  Marco Ponassi⁴  Camillo Rosano⁴  Lamberto Felli⁴ 

[1] Breast Cancer Unit, Regional Hospital, Cosenza 87100, Italy;Department of Chemical Sciences, University of Messina, Messina 98166, Italy;Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Rende 87036, Italy;U.O.S. Biopolymers and Proteomics, IST-National Institute for Cancer Research, Genova 16132, Italy;

关键词: Breast cancer;    Calixpyrroles;    Cancer-associated fibroblasts;    Estrogen;    GPR30/GPER;    Signal transduction;   

DOI  :  10.1242/dmm.021071

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown