{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:59:28Z","timestamp":1789131568139,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015694","name":"Fondazione Cassa di Risparmio di Firenze","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p>Endometriosis is a chronic gynecological syndrome characterized by endometrial cell invasion of the extra\u2010uterine milieu, pelvic pain and infertility. Treatment relies on either symptomatic drugs or hormonal therapies, even though the mechanism involved in the onset of endometriosis is yet to be elucidated. The signaling of sphingolipid sphingosine 1\u2010phosphate (S1P) is profoundly dysregulated in endometriosis. Indeed, sphingosine kinase (SK)1, one of the two isoenzymes responsible for S1P biosynthesis, and S1P<jats:sub>1<\/jats:sub>, S1P<jats:sub>3<\/jats:sub> and S1P<jats:sub>5<\/jats:sub>, three of its five specific receptors, are more highly expressed in endometriotic lesions compared to healthy endometrium. Recently, missense coding variants of the gene encoding the receptor 1 for neuropeptide S (NPS) have been robustly associated with endometriosis in humans. This study aimed to characterize the biological effect of NPS in endometriotic epithelial cells and the possible involvement of the S1P signaling axis in its action. NPS was found to potently induce cell invasion and actin cytoskeletal remodeling. Of note, the NPS\u2010induced invasive phenotype was dependent on SK1 and SK2 as well as on S1P<jats:sub>1<\/jats:sub> and S1P<jats:sub>3<\/jats:sub>, given that the biological action of the neuropeptide was fully prevented when one of the two biosynthetic enzymes or one of the two selective receptors was inhibited or silenced. Furthermore, the RhoA\/Rho kinase pathway, downstream to S1P receptor signaling, was found to be critically implicated in invasion and cytoskeletal remodeling elicited by NPS. These findings provide new information to the understanding of the molecular mechanisms implicated in endometriosis pathogenesis, establishing the rationale for non\u2010hormonal therapeutic targets for its treatment.<\/jats:p>","DOI":"10.1111\/febs.17071","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T04:39:27Z","timestamp":1706589567000},"page":"1744-1758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Sphingosine 1\u2010phosphate signaling axis mediates neuropeptide S\u2010induced invasive phenotype of endometriotic cells"],"prefix":"10.1111","volume":"291","author":[{"given":"Matteo","family":"Prisinzano","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-0067","authenticated-orcid":false,"given":"Caterina","family":"Bernacchioni","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Seidita","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Raeispour","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cencetti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Vannuccini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Fambrini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Petraglia","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2224-4199","authenticated-orcid":false,"given":"Chiara","family":"Donati","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.041"},{"key":"e_1_2_11_3_1","first-page":"93","article-title":"Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation","volume":"3","author":"Sampson JA","year":"1927","journal-title":"Am J Pathol"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719116660847"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey391"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1810764"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-021-09666-w"},{"key":"e_1_2_11_8_1","article-title":"Nonsteroidal anti\u2010inflammatory drugs for pain in women with endometriosis","volume":"2017","author":"Brown J","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1340"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-023-01167-2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.08.012"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202300323R"},{"key":"e_1_2_11_13_1","first-page":"1519","article-title":"Sphingosine 1\u2010phosphate (S1P) in the peritoneal fluid skews M2 macrophage and contributes to the development of endometriosis","volume":"9","author":"Ono Y","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15601"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2023.12.007"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.107"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2011.09.003"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2015.09.001"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd6469"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.12.051"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg540"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609559200"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.33.20685"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-09-0812"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2006.02615.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.06.012"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009315"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-014-1602-x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.10.013"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2013.10.030"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-274340"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410144200"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.24.14196"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.11.016"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.96"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502207200"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-2-15"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11040713"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502922200"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01465-07"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12070980"},{"key":"e_1_2_11_42_1","first-page":"1619","article-title":"Sphingosine\u20101\u2010phosphate receptor\u20103 signaling up\u2010regulates epidermal growth factor receptor and enhances epidermal growth factor receptor\u2010mediated carcinogenic activities in cultured\u00a0lung adenocarcinoma cells","volume":"40","author":"Lee M\u2010J","year":"2012","journal-title":"Int J Oncol"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0223"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2006.01.006"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvh081"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-12-0092"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801635R"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0427OC"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13423"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.09.004"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15689"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3248"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2016.160"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-023-02618-5"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2012.10.010"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2017.02.004"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16579"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2022.03.026"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2018.12.007"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.17071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T06:02:42Z","timestamp":1735279362000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.17071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,29]]},"references-count":59,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/febs.17071"],"URL":"https:\/\/doi.org\/10.1111\/febs.17071","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,29]]},"assertion":[{"value":"2023-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}