{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:00:13Z","timestamp":1785304813357,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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":["Cancer Reports"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accumulating evidence indicates a critical role of androgen receptor (AR) in the pathogenesis of male\u2010dominant urothelial cancer. Meanwhile, the functions of latrophilins (LPHNs), a subfamily of G protein\u2010coupled receptors, remain largely uncharacterized in neoplastic conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To determine the functional role of LPHN1 and LPHN2 in association with AR signaling in urothelial tumorigenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      AR overexpression in immortalized human normal urothelial SVHUC cells or androgen treatment in SVHUC\u2010AR cells markedly increased the expression levels of LPHN1 and LPHN2. Chromatin immunoprecipitation assay demonstrated that AR could bind to the promoter regions of their encoded genes,\n                      <jats:italic>ADGRL1<\/jats:italic>\n                      and\n                      <jats:italic>ADGRL2<\/jats:italic>\n                      . In SVHUC\u2010AR cells exposed to a chemical carcinogen 3\u2010methylcholanthrene to induce neoplastic transformation, shRNA\u2010mediated knockdown of LPHN1 or LPHN2 significantly reduced their oncogenic activity, as measured by the ability of the resultant cells to form colonies and migrate. Immunohistochemistry in surgical specimens further revealed significantly higher levels of LPHN1 and LPHN2 expression in non\u2010muscle\u2010invasive bladder tumors than in adjacent non\u2010neoplastic urothelial tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The present findings suggest that LPHN1 and LPHN2 function as downstream mediators of AR signaling and promote urothelial tumorigenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70624","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:01:53Z","timestamp":1784109713000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Latrophilin\u20101 and Latrophilin\u20102 as Downstream Effectors of Androgen Receptor Signaling in Urothelial Tumorigenesis"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-5049","authenticated-orcid":false,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8620-0710","authenticated-orcid":false,"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":"Mohammad Amin","family":"Elahi Najafi","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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Wilmot Cancer Institute University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Urology University of Rochester Medical Center  Rochester New York USA"},{"name":"Department of Pathology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21262"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djk113"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082155"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2023.2203388"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.08.005"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-023-04640-2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.38.23239"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1598"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/bmc-2014-0032"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.49.32715"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.504779"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-20-0050"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23783"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.62347\/KFGI9710"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-024-01324-2"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.21833"},{"key":"e_1_2_11_19_1","first-page":"2325","article-title":"ELK1 Promotes Urothelial Tumorigenesis in the Presence of an Activated Androgen Receptor","volume":"8","author":"Inoue S.","year":"2018","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-20-0004"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241813733"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/9.8.1427"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2011.10706.x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.05.004"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2069"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.642"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2015.153"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.4149\/gpb_2018008"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01594"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-021-00721-3"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.01.018"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091466"}],"container-title":["Cancer Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70624","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cnr2.70624","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70624","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:14:16Z","timestamp":1785302056000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cnr2.70624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/cnr2.70624"],"URL":"https:\/\/doi.org\/10.1002\/cnr2.70624","archive":["Portico"],"relation":{},"ISSN":["2573-8348","2573-8348"],"issn-type":[{"value":"2573-8348","type":"print"},{"value":"2573-8348","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70624"}}