{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:03:30Z","timestamp":1784153010022,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100016930","name":"Ferring Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016930","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Emerging evidence indicates that androgen receptor (AR) signaling plays a critical role in the pathogenesis of male\u2010dominant urothelial cancer. Meanwhile, latrophilins (LPHNs), a group of the G\u2010protein\u2010coupled receptor to which a spider venom latrotoxin is known to bind, remain largely uncharacterized in neoplastic diseases. The present study aimed to determine the functional role of LPHN3 (encoded by the <jats:italic>ADGRL3<\/jats:italic> gene), in association with AR signaling, in urothelial tumorigenesis. In human normal urothelial SVHUC cells, AR overexpression and androgen treatment considerably increased the expression levels of <jats:italic>ADGRL3<\/jats:italic>\/LPHN3, while chromatin immunoprecipitation assay revealed the binding of AR to the promoter region of <jats:italic>ADGRL3<\/jats:italic>. In SVHUC or SVHUC\u2010AR cells with exposure to a chemical carcinogen 3\u2010methylcholanthrene, LPHN3 activation via ligand (e.g., \u03b1\u2010latrotoxin, FLRT3) treatment during the process of the neoplastic\/malignant transformation or LPHN3 knockdown via shRNA virus infection induced or reduced, respectively, the oncogenic activity. In <jats:italic>N<\/jats:italic>\u2010butyl\u2010<jats:italic>N<\/jats:italic>\u2010(4\u2010hydroxybutyl)nitrosamine\u2010treated female mice, \u03b1\u2010latrotoxin or FLRT3 injection accelerated the development of bladder tumors. Immunohistochemistry in surgical specimens further showed the significantly elevated expression of LPHN3 in non\u2010muscle\u2010invasive bladder tumors, compared with adjacent normal urothelial tissues, which was associated with a marginally (<jats:italic>p<\/jats:italic>\u2009=\u20090.051) higher risk of disease recurrence after transurethral resection. In addition, positivity of LPHN3 and AR in these tumors was strongly correlated. These findings indicate that LPHN3 functions as a downstream effector of AR and promotes urothelial tumorigenesis.<\/jats:p>","DOI":"10.1002\/mc.23783","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T13:35:25Z","timestamp":1719236125000},"page":"1847-1854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Latrophilin\u20103 as a downstream effector of the androgen receptor induces urothelial tumorigenesis"],"prefix":"10.1002","volume":"63","author":[{"given":"Takuro","family":"Goto","sequence":"first","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Rochester Medical Center Rochester New York USA"},{"name":"James P. Wilmot Cancer Institute University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Yasui","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Rochester Medical Center Rochester New York USA"},{"name":"James P. Wilmot Cancer Institute University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Teramoto","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Rochester Medical Center Rochester New York USA"},{"name":"James P. Wilmot Cancer Institute University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Rochester Medical Center Rochester New York USA"},{"name":"James P. Wilmot Cancer Institute University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichi","family":"Mizushima","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine University of Rochester Medical Center Rochester New York USA"},{"name":"James P. 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