{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:24:14Z","timestamp":1791923054958,"version":"4.3.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Fujian Provincial Natural Science Foundation of China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Advanced bladder cancer (bc) patients often have poor prognoses due to issues such as recurrence and drug resistance. The discovery of ferroptosis has opened new avenues for bc treatment; however, the specific regulatory mechanisms remain to be explored. This study aimed to investigate the mechanisms influencing ferroptosis in bc cells, with a particular focus on the role of low-density lipoprotein receptor-related protein 8 (LRP8).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized reverse transcription-quantitative polymerase chain reaction and western blot to assess the expression of LRP8 in bc cells, activation of the Wnt\/\u03b2-catenin signaling pathway, and the expression of genes related to fatty acid synthesis. We measured changes in ferroptosis levels by evaluating mitochondrial membrane potential, Fe2+, malondialdehyde, and reactive oxygen species levels. A xenograft mouse model was employed to validate the impact of LRP8 on bc progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cell experiments demonstrated a significant upregulation of LRP8 expression in bc cells. Knockdown of LRP8 induced ferroptosis in bc cells, a process directly triggered by the inhibition of the Wnt\/\u03b2-catenin signaling pathway. Activation of the Wnt\/\u03b2-catenin signaling pathway mediated by LRP8 upregulated the expression of stearoyl-CoA desaturase 1 (SCD1), subsequently leading to the suppression of ferroptosis. In vivo experiments indicated that LRP8 knockdown significantly impaired bc growth, accompanied by inhibition of the Wnt\/\u03b2-catenin-SCD1 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LRP8 mediates the synthesis of monounsaturated fatty acids through the Wnt\/\u03b2-catenin-SCD1 positive feedback loop, thereby inhibiting ferroptosis in bc cells. These findings provide a promising target for the regulation of ferroptosis in bc cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/hmg\/ddaf024","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T07:27:17Z","timestamp":1738826837000},"page":"843-851","source":"Crossref","is-referenced-by-count":4,"title":["LRP8 inhibits bladder cancer cell ferroptosis by activating the Wnt\/\u03b2-catenin-SCD1 positive feedback loop"],"prefix":"10.1093","volume":"34","author":[{"given":"Yong","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Urology, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijun","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9106-4547","authenticated-orcid":false,"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanping First Hospital Affiliated to Fujian Medical University , No. 317 Zhongshan Road, Yanping District, Nanping City, Fujian Province 353000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"2025052713402746400_ref1","article-title":"Bladder cancer: current challenges and future directions","volume":"57","author":"Dobruch","year":"2021","journal-title":"Med (Kaunas)"},{"key":"2025052713402746400_ref2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.urology.2005.07.062","article-title":"Bladder cancer: epidemiology, staging and grading, and diagnosis","volume":"66","author":"Kirkali","year":"2005","journal-title":"Urology"},{"key":"2025052713402746400_ref3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"2025052713402746400_ref4","doi-asserted-by":"crossref","first-page":"631152","DOI":"10.3389\/fmolb.2021.631152","article-title":"Biological functions and prognostic value of Ferroptosis-related genes in bladder cancer","volume":"8","author":"Yi","year":"2021","journal-title":"Front Mol Biosci"},{"key":"2025052713402746400_ref5","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.euf.2023.04.006","article-title":"Pelvic organ preservation in non-muscle-invasive bladder cancer: less is more","volume":"9","author":"Faulk","year":"2023","journal-title":"Eur Urol Focus"},{"key":"2025052713402746400_ref6","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jacbts.2021.09.011","article-title":"Interplay of low-density lipoprotein receptors, LRPs, and lipoproteins in pulmonary hypertension","volume":"7","author":"Calvier","year":"2022","journal-title":"JACC Basic Transl Sci"},{"key":"2025052713402746400_ref7","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23168921","article-title":"Low-density lipoprotein receptor-related protein 8 at the crossroad between cancer and neurodegeneration","volume":"23","author":"Passarella","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2025052713402746400_ref8","doi-asserted-by":"crossref","first-page":"101284","DOI":"10.1016\/j.tranon.2021.101284","article-title":"miR-362-3p suppresses ovarian cancer by inhibiting LRP8","volume":"15","author":"Li","year":"2022","journal-title":"Transl Oncol"},{"key":"2025052713402746400_ref9","doi-asserted-by":"crossref","first-page":"6807","DOI":"10.1080\/21655979.2022.2036917","article-title":"Low-density lipoprotein receptor-related protein 8 facilitates the proliferation and invasion of non-small cell lung cancer cells by regulating the Wnt\/beta-catenin signaling pathway","volume":"13","author":"Fang","year":"2022","journal-title":"Bioengineered"},{"key":"2025052713402746400_ref10","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.canlet.2018.09.022","article-title":"Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer","volume":"438","author":"Lin","year":"2018","journal-title":"Cancer Lett"},{"key":"2025052713402746400_ref11","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cellsig.2019.05.009","article-title":"Estrogen receptor alpha regulates the Wnt\/beta-catenin signaling pathway in colon cancer by targeting the NOD-like receptors","volume":"61","author":"Liu","year":"2019","journal-title":"Cell Signal"},{"key":"2025052713402746400_ref12","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: an iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"2025052713402746400_ref13","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20210518","article-title":"Ferroptosis in infection, inflammation, and immunity","volume":"218","author":"Chen","year":"2021","journal-title":"J Exp Med"},{"key":"2025052713402746400_ref14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41419-020-2298-2","article-title":"Ferroptosis: past, present and future","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis"},{"key":"2025052713402746400_ref15","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41568-022-00459-0","article-title":"Targeting ferroptosis as a vulnerability in cancer","volume":"22","author":"Lei","year":"2022","journal-title":"Nat Rev Cancer"},{"key":"2025052713402746400_ref16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41419-023-05614-5","article-title":"SGK2 promotes prostate cancer metastasis by inhibiting ferroptosis via upregulating GPX4","volume":"14","author":"Cheng","year":"2023","journal-title":"Cell Death Dis"},{"key":"2025052713402746400_ref17","doi-asserted-by":"crossref","first-page":"102317","DOI":"10.1016\/j.redox.2022.102317","article-title":"Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer","volume":"52","author":"Ouyang","year":"2022","journal-title":"Redox Biol"},{"key":"2025052713402746400_ref18","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.7150\/ijbs.74546","article-title":"PHGDH inhibits Ferroptosis and promotes malignant progression by upregulating SLC7A11 in bladder cancer","volume":"18","author":"Shen","year":"2022","journal-title":"Int J Biol Sci"},{"key":"2025052713402746400_ref19","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41392-020-00216-5","article-title":"The interaction between ferroptosis and lipid metabolism in cancer","volume":"5","author":"Li","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"2025052713402746400_ref20","doi-asserted-by":"crossref","first-page":"832892","DOI":"10.3389\/fcell.2022.832892","article-title":"Ferroptosis patterns and tumor microenvironment infiltration characterization in bladder cancer","volume":"10","author":"Xia","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"2025052713402746400_ref21","doi-asserted-by":"crossref","first-page":"1043283","DOI":"10.3389\/fphar.2022.1043283","article-title":"Ferroptosis: a new therapeutic target for bladder cancer","volume":"13","author":"Zeng","year":"2022","journal-title":"Front Pharmacol"},{"key":"2025052713402746400_ref22","article-title":"FLRT2 suppresses bladder cancer progression through inducing ferroptosis","volume":"28","author":"Jiang","year":"2023","journal-title":"J Cell Mol Med"},{"key":"2025052713402746400_ref23","article-title":"Enhanced LRP8 expression induced by helicobacter pylori drives gastric cancer progression by facilitating beta-catenin nuclear translocation","author":"Liu","year":"2024","journal-title":"J Adv Res"},{"key":"2025052713402746400_ref24","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22010330","article-title":"Monounsaturated fatty acids in obesity-related inflammation","volume":"22","author":"Ravaut","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2025052713402746400_ref25","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s13046-021-02067-6","article-title":"SCD1, autophagy and cancer: implications for therapy","volume":"40","author":"Ascenzi","year":"2021","journal-title":"J Exp Clin Cancer Res"},{"key":"2025052713402746400_ref26","doi-asserted-by":"crossref","first-page":"102006","DOI":"10.1016\/j.redox.2021.102006","article-title":"Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and fatty acid biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence","volume":"43","author":"Luis","year":"2021","journal-title":"Redox Biol"},{"key":"2025052713402746400_ref27","doi-asserted-by":"crossref","first-page":"101807","DOI":"10.1016\/j.redox.2020.101807","article-title":"FBW7-NRA41-SCD1 axis synchronously regulates apoptosis and ferroptosis in pancreatic cancer cells","volume":"38","author":"Ye","year":"2021","journal-title":"Redox Biol"},{"key":"2025052713402746400_ref28","doi-asserted-by":"crossref","first-page":"15374","DOI":"10.18632\/aging.103598","article-title":"Stearoyl-CoA desaturase 1 (SCD1) facilitates the growth and anti-ferroptosis of gastric cancer cells and predicts poor prognosis of gastric cancer","volume":"12","author":"Wang","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"2025052713402746400_ref29","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1007\/s12033-023-00843-7","article-title":"METTL14 suppresses tumor Stemness and metastasis of colon cancer cells by modulating m6A-modified SCD1","volume":"66","author":"Xu","year":"2023","journal-title":"Mol Biotechnol"},{"key":"2025052713402746400_ref30","doi-asserted-by":"crossref","first-page":"e752","DOI":"10.1002\/ctm2.752","article-title":"Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1-Wnt\/beta-catenin-TFE3 feedback loop signalling","volume":"12","author":"Luo","year":"2022","journal-title":"Clin Transl Med"},{"key":"2025052713402746400_ref31","doi-asserted-by":"crossref","first-page":"e004616","DOI":"10.1136\/jitc-2022-004616","article-title":"Inhibition of stearoyl-CoA desaturase 1 (SCD1) enhances the antitumor T cell response through regulating beta-catenin signaling in cancer cells and ER stress in T cells and synergizes with anti-PD-1 antibody","volume":"10","author":"Katoh","year":"2022","journal-title":"J Immunother Cancer"},{"key":"2025052713402746400_ref32","doi-asserted-by":"crossref","DOI":"10.3390\/cells11223580","article-title":"Targeting Wnt\/beta-catenin Signaling exacerbates Ferroptosis and increases the efficacy of melanoma immunotherapy via the regulation of MITF","volume":"11","author":"Wang","year":"2022","journal-title":"Cells"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/34\/10\/843\/62083382\/ddaf024.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/34\/10\/843\/62083382\/ddaf024.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T13:40:37Z","timestamp":1748353237000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/34\/10\/843\/8034847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,24]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,2,24]]},"published-print":{"date-parts":[[2025,5,6]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddaf024","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5,15]]},"published":{"date-parts":[[2025,2,24]]}}}