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Soluble factors secreted by cancer and stromal cells contribute to stroma remodeling through the secretion of ECM proteins, providing a favorable environment for cancer cell dissemination. The peptide endothelin-1 (ET-1), through two G protein-coupled receptors (GPCR), endothelin receptor type A (ET<jats:sub>A<\/jats:sub>R) and B (ET<jats:sub>B<\/jats:sub>R), acts on both cancer and stromal cells, engaging the protein \u03b2-arrestin1 (\u03b2-arr1), to bolster SOC progression. However, its role in the regulation of the ECM proteins by ovarian fibroblasts is not understood. This study delves into the role of ET-1 as a regulator of type I collagen (Col1) and fibronectin (FN).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We used human primary ovarian fibroblasts (HOFs) and CAFs. The expression of Col1 (<jats:italic>COL1A1<\/jats:italic>) and FN (<jats:italic>FN1<\/jats:italic>) were detected by western blotting (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and confocal laser scanning microscopy (CLSM) in cells and tumor tissue sections from mice xenografts, while the transcription of <jats:italic>COL1A1<\/jats:italic> was detected by luciferase reporter gene assay. The nuclear function of \u03b2-arr1 was evaluated by silencing and rescue expression with wild-type (WT) and nuclear mutant plasmid constructs, RNA seq and differential gene expression and gene sets enrichment analyses. The prognostic role of <jats:italic>COL1A1<\/jats:italic>,<jats:italic> FN1<\/jats:italic>,<jats:italic> EDN1<\/jats:italic> (ET-1) and <jats:italic>ARRB1<\/jats:italic> (\u03b2-arr1) gene expression was evaluated using the Kaplan\u2013Meier plotter database and clinical ovarian cancer tissue samples.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We demonstrated that ET-1 boosts Col1 and FN expression in HOFs, akin to ovarian CAF levels. Both receptors are implicated, evident from inhibitory effects after ET<jats:sub>A<\/jats:sub>R or ET<jats:sub>B<\/jats:sub>R antagonist treatments and notably with bosentan, a dual antagonist, in vitro and in vivo. At the molecular level, ET-1 triggers the activation of <jats:italic>COL1A1<\/jats:italic> promoter activity and its enhanced expression via \u03b2-arr1 nuclear function. Transcriptome analysis of \u03b2-arr1-silenced HOFs confirms the nuclear role of \u03b2-arr1 in collagen and ECM remodeling-related protein transcriptional regulation. Accordingly, a high level of <jats:italic>EDN1\/ARRB1<\/jats:italic> expression in combination with either <jats:italic>COL1A1<\/jats:italic> or <jats:italic>FN1<\/jats:italic> is associated with the poor prognosis of SOC patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These findings hint at ET-1 involvement in ECM remodeling and early SOC stages by modulating the expression of Col1 and FN. Targeting ET-1 signaling with ET<jats:sub>A<\/jats:sub>R\/ET<jats:sub>B<\/jats:sub>R antagonists might interfere with the ability of CAFs to produce key ECM proteins in this tumor.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13046-025-03327-5","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:02:45Z","timestamp":1740121365000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The extracellular matrix protein type I collagen and fibronectin are regulated by \u03b2-arrestin-1\/endothelin axis in human ovarian fibroblasts"],"prefix":"10.1186","volume":"44","author":[{"given":"Ilenia","family":"Masi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Ottavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Caprara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danila Del","family":"Rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Kunkl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Spadaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Licursi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta","family":"Tuosto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bagnato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9962-6411","authenticated-orcid":false,"given":"Laura","family":"Rosano\u2019","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"3327_CR1","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.devcel.2019.03.026","volume":"49","author":"F Kai","year":"2019","unstructured":"Kai F, Drain AP, Weaver VM. 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