{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T15:12:54Z","timestamp":1771081974475,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Megalin (LRP2) is a multifunctional endocytic receptor whose role in prostate cancer (PCa), particularly in cancer stem cells (CSCs) and metastatic progression, remains largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed LRP2 mRNA and protein expression in DU\u2010145, PC\u20103, and RWPE1 cells and their CD133\n                      <jats:sup>high<\/jats:sup>\n                      \/CD44\n                      <jats:sup>high<\/jats:sup>\n                      CSCs via qRT\u2010PCR and immunofluorescence, in both 2D and 3D cultures. Public RNA\u2010seq data (TCGA, WCDT\u2010MCRPC) were used to assess LRP2, CD133, and CD44 across normal, primary, and metastatic tumors. Gene Set Enrichment Analysis (GSEA) and correlation with AR, VDR, and stemness genes were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>LRP2 was significantly upregulated in DU\u2010145 cells and CSCs in the 3D culture system. In contrast, PC\u20103 CSCs showed reduced LRP2 expression. In clinical datasets, LRP2 was highest in metastatic tumors (log2FC\u2009=\u20093.58), with bone (M1B) and other parts of the body (M1C) subtypes exhibiting elevated levels compared to primary tumors. CD133 was consistently downregulated in metastases. GSEA highlighted LRP2 involvement in lipid, retinoid, and steroid metabolism. LRP2 correlated positively with VDR and negatively with AR in M1C tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LRP2 shows subtype\u2010specific expression patterns in PCa, with elevated levels in DU\u2010145 CSCs and metastatic tumors. Its link to metabolic pathways and inverse relationship with AR suggest a potential role in therapy resistance and metastasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70105","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T08:00:05Z","timestamp":1764835205000},"page":"464-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Megalin (LRP2) Expression Patterns in Prostate Cancer Stem Cells and Metastatic Subtypes: Implications for Tumor Progression and Metabolism"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3374-9272","authenticated-orcid":false,"given":"Gunel","family":"Mukhtarova","sequence":"first","affiliation":[{"name":"Department of Basic Oncology, Graduate School of Health Sciences Ege University Izmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aysegul","family":"Murat","sequence":"additional","affiliation":[{"name":"Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cigir","family":"Biray Avci","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Ege University Izmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eda","family":"Acikgoz","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Van Yuzuncu Yil University Van Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4150-8495","authenticated-orcid":false,"given":"Huseyin","family":"Aktug","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Ege University Izmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulperi","family":"Oktem","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Ege University Izmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-00907-4"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08290-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2018"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-021-06387-w"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14215448"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2016.0877"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-025-10398-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00022.2012"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod55.3.676"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0578fje"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V104685"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26497"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.4067\/S0716-97602011000100012"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91054"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2847-3"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","unstructured":"F.Cabezas P.Farf\u00e1n andM. 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