{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:12:58Z","timestamp":1785420778069,"version":"3.56.0"},"reference-count":154,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER funds","award":["007491"],"award-info":[{"award-number":["007491"]}]},{"name":"FEDER funds","award":["029114"],"award-info":[{"award-number":["029114"]}]},{"name":"National Funds by FCT-Foundation for Science and Technology","award":["UID\/Multi\/00709\/2019"],"award-info":[{"award-number":["UID\/Multi\/00709\/2019"]}]},{"name":"FCT","award":["SFRH\/BD\/104671\/2014"],"award-info":[{"award-number":["SFRH\/BD\/104671\/2014"]}]},{"award":["SFRH\/BD\/104671\/2014"],"award-info":[{"award-number":["SFRH\/BD\/104671\/2014"]}],"id":[{"id":"https:\/\/ror.org\/00bh4be42","id-type":"ROR","asserted-by":"publisher"}]},{"name":"FCT","award":["SFRH\/BD\/111351\/2015"],"award-info":[{"award-number":["SFRH\/BD\/111351\/2015"]}]},{"award":["SFRH\/BD\/111351\/2015"],"award-info":[{"award-number":["SFRH\/BD\/111351\/2015"]}],"id":[{"id":"https:\/\/ror.org\/00bh4be42","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The G protein-coupled oestrogen receptor (GPER) has anti-tumorigenic effects in several human cancers. However, its role in prostate cancer (PCa) remains incompletely defined. The present study investigated GPER\u2019s role in targeting the hallmarks of PCa. Methods: Tissue microarrays were used to analyse GPER immunoexpression in PCa samples. Non-neoplastic (PNT1A) and neoplastic (LNCaP, DU145 and PC3) prostate cells were treated with the GPER-specific agonist, G1. Cell viability, proliferation, cell cycle, apoptosis, migration and invasion were evaluated. Glucose consumption, lactate production, lactate dehydrogenase activity and oxidative status were determined spectrophotometrically. Results: GPER immunoreactivity was higher in PCa than in benign prostatic hyperplasia and inversely correlated with PSA serum levels. G1 modulated GPER subcellular location in prostate cells, being detected at the cell membrane, endoplasmic reticulum, and residually in the nucleus. GPER activation decreased cell viability and proliferation, induced cell cycle arrest at G2\/M phase, and increased PCa cells apoptosis. Additionally, GPER activation inhibited the migration and invasion of DU145 cells, and long-term exposure to G1 reduced epithelial\u2013mesenchymal transition, an effect not observed in PC3 cells, indicating the importance of cell-specific contexts. Our results also showed that G1 treatment modulated the metabolic profile of PCa cells, changing glucose, amino acids and lipid metabolism. Finally, G1 increased oxidative stress in PCa cells. Conclusions: Overall, this study demonstrated that GPER activation affects a broad range of PCa hallmarks. These findings support an anti-cancer role for GPER in PCa and encourage further exploration of its action in regulating metabolism and as a therapeutic target.<\/jats:p>","DOI":"10.3390\/cancers18071137","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T14:59:01Z","timestamp":1775055541000},"page":"1137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["G Protein-Coupled Oestrogen Receptor Actions Targeting the Hallmarks of Cancer in Human Prostate Cells: From Cell Fate to Metabolic Reprogramming"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0901-9931","authenticated-orcid":false,"given":"Mar\u00edlia I.","family":"Figueira","sequence":"first","affiliation":[{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-2875","authenticated-orcid":false,"given":"Henrique J.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8789-4048","authenticated-orcid":false,"given":"Lara R. S.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Chemistry, Faculty of Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago M. A.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9199-8360","authenticated-orcid":false,"given":"Sara","family":"Correia","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Arinto","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO Porto Research Center (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center, 4200-072 Porto, Portugal"},{"name":"Department of Laboratory Genetics, Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center, 4200-072 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cancer Biology and Epigenetics Group\u2014Research Center, Portuguese Oncology Institute of Porto\/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-9191","authenticated-orcid":false,"given":"Adriana O.","family":"Santos","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5658-5445","authenticated-orcid":false,"given":"Cl\u00e1udio J.","family":"Maia","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-488X","authenticated-orcid":false,"given":"S\u00edlvia","family":"Socorro","sequence":"additional","affiliation":[{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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