{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:08:54Z","timestamp":1778803734447,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP 23K08759"],"award-info":[{"award-number":["JP 23K08759"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Approximately 83,000 new cases of bladder cancer (BC) in the United States and 23,000 in Japan are confirmed per year, and the number of new BC cases increases every year. While the prognosis for localized cancer is favorable, treatment options for metastatic cancer are limited, and the prognosis is extremely poor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Although the prevention of metastasis and the development of novel treatments for metastatic cancer are urgent challenges, the molecules contributing to BC metastasis and prognosis remain largely unknown. This study aimed to identify and analyze novel therapeutic target molecules for metastatic BC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We collected gene expression datasets for BC cell lines from Gene Expression Omnibus and selected genes highly expressed in advanced BC cell lines. We also extracted genes highly expressed in metastatic BC patients from The Cancer Genome Atlas. We performed integrated analysis on these genes and combined it with Kaplan\u2010Meier analysis to identify genes involved in BC progression. The results revealed that CDH11 is involved in bladder cancer progression. We established CDH11 knockdown (KD) using shRNA in advanced bladder cancer cell lines and performed analyses of cell proliferation, invasion, and migration; gene expression analysis via RNA\u2010seq; tumor formation via xenografts; metabolic analysis using the Flux analyzer; and therapeutic effect analysis using low\u2010molecular\u2010weight compounds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>While CDH11 KD did not alter cell proliferation, invasion, or migration in\u00a0vitro, CDH11 KD significantly suppressed tumor growth in an in\u00a0vivo subcutaneous xenograft mouse model. RNA\u2010seq revealed that CDH11 KD cells decreased the expression of genes related to mitochondrial metabolism, and a metabolic flux analyzer confirmed decreased mitochondrial activity in the KD cells. Furthermore, use of a CDH11 inhibitor resulted in decreased mitochondrial activity in\u00a0vitro, and CDH11 inhibitor resulted in inhibition of tumor growth in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings suggest that CDH11 is highly expressed in advanced BC and may regulate the TME by interacting with other cell types and regulating mitochondrial energy metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results suggest that CDH11 is involved in BC progression and is a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71399","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T11:22:53Z","timestamp":1763637773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>CDH11<\/scp>\n                    Contributes to Bladder Cancer Progression via Regulation of Mitochondrial Energy Metabolism"],"prefix":"10.1002","volume":"14","author":[{"given":"Osuke","family":"Arai","sequence":"first","affiliation":[{"name":"Department of Urology Ehime University Graduate School of Medicine  Toon Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Yanagihara","sequence":"additional","affiliation":[{"name":"Division of Integrative Pathophysiology Proteo\u2010Science Center, Ehime University  Toon Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruna","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Urology Ehime University Graduate School of Medicine  Toon Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuta","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Urology Ehime University Graduate School of Medicine  Toon Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2229-0948","authenticated-orcid":false,"given":"Noriyoshi","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Urology Ehime University Graduate School of Medicine  Toon Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadahiko","family":"Kikugawa","sequence":"additional","affiliation":[{"name":"Department of Urology Ehime University Graduate School of Medicine  Toon Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Saika","sequence":"additional","affiliation":[{"name":"Department of Urology Ehime University Graduate School of Medicine  Toon Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6119-0034","authenticated-orcid":false,"given":"Yuuki","family":"Imai","sequence":"additional","affiliation":[{"name":"Division of Integrative Pathophysiology Proteo\u2010Science Center, Ehime University  Toon Japan"},{"name":"Department of Pathophysiology Ehime University Graduate School of Medicine  Toon Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3817"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyq167"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12525"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2018.01.009"},{"key":"e_1_2_13_7_1","first-page":"1","article-title":"Omics Sciences and Precision Medicine in Urothelial Carcinoma","volume":"174","author":"Medori M. 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