Fernández-Nogueira, PatriciaNoguera Castells, AleixFuster Orellana, GemmaRecalde Percaz, LeireMoragas, NúriaLópez Plana, AnnaEnreig, EstelJauregui, PatriciaCarbó Carbó, NeusAlmendro Navarro, VanessaGascón, PereBragado Domingo, PalomaMancino, Mario2024-02-132024-02-132018-06-280304-3835https://hdl.handle.net/2445/207550Histamine receptor 1 (HRH1) belongs to the rhodopsin-like G-protein-coupled receptor family. Its activation by histamine triggers cell proliferation, embryonic development, and tumor growth. We recently established that HRH1 is up-regulated in basal and human epidermal growth factor receptor 2 (HER2)-enriched human breast tumors and that its expression correlates with a worse prognosis. Nevertheless, the functional role of HRH1 in basal and HER2-targeted therapy-resistant breast cancer (BC) progression has not yet been addressed. Using terfenadine, a selective chemical inhibitor of HRH1, we showed that the inhibition of HRH1 activity in basal BC cells leads to sub-G0 cell accumulation, suppresses proliferation, promotes cell motility and triggers the activation of extracellular signal-regulated kinase (ERK) signaling, initiating the mitochondrial apoptotic pathway. Furthermore, HER2-targeted therapy-resistant cells express higher levels of HRH1 and are more sensitive to terfenadine treatment. Moreover, in vivo experiments showed that terfenadine therapy reduced the tumor growth of basal and trastuzumab-resistant BC cells. In conclusion, our results suggest that targeting HRH1 is a promising new clinical approach to consider that could enhance the effectiveness of current therapeutic treatment in patients with basal and BC tumors resistant to HER2-targeted therapies.14 p.application/pdfengcc-by-nc-nd (c) Fernandez-Nogueira, Patricia et al., 2018http://creativecommons.org/licenses/by-nc-nd/4.0/Receptors cel·lularsApoptosiNeuropèptidsInhibidors enzimàticsCàncer de mamaHistaminaCell receptorsApoptosisNeuropeptidesEnzyme inhibitorsBreast cancerHistamineinfo:eu-repo/semantics/article6901052024-02-13info:eu-repo/semantics/openAccess29548821