{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:06:41Z","timestamp":1779782801159,"version":"3.53.1"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372966"],"award-info":[{"award-number":["82372966"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In males, prostate cancer (PCa) is one of the frequently diagnosed forms of cancer, with high clinical variability and limited treatment options for advanced cases. This receptor, which goes by the names Coagulation Factor II Receptor (F2R) and PAR1, belongs to the family of G\u2010protein\u2010linked membrane proteins and plays roles in both blood clotting processes and the development of malignancies. Whereas F2R has been associated with tumor progression in various malignancies, its specific involvement in PCa is not well understood. Here, we seek to examine the expression patterns and biological functions of F2R to better understand its impact on PCa progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically analyzed F2R expression in PCa using data from the TCGA database and clinical specimens. Functional experiments, including cell proliferation, invasion, and apoptosis assays, were conducted in PCa cell lines with F2R overexpression or knockdown. Bioinformatics analyses were performed to identify F2R\u2010associated genes and signaling pathways. In\u00a0vivo xenograft models were used to validate the oncogenic role of F2R.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrated that F2R is significantly overexpressed in PCa tissues and correlates with advanced clinicopathological features such as higher T stage, nodal metastasis, and elevated Gleason scores. Functional studies revealed that F2R promotes PCa cell proliferation, invasion, and cell cycle progression while inhibiting apoptosis. Mechanistically, we identified collagen type VIII alpha 1 (COL8A1) as a key downstream effector of F2R, which activates the FAK\/PI3K\/AKT signaling pathway. In\u00a0vivo experiments confirmed that F2R knockdown suppresses tumor growth and downregulates this signaling axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study highlights F2R as an important promoter in PCa progression and identifies the F2R\u2010COL8A1\u2010FAK\/PI3K\/AKT signaling axis as a potential molecular mechanism underlying tumor aggressiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgm.70097","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:11:46Z","timestamp":1778681506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["F2R Promotes Prostate Cancer Progression via COL8A1\u2010Dependent Activation of the FAK\/PI3K\/AKT Signaling Axis"],"prefix":"10.1002","volume":"28","author":[{"given":"Xianfan","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Urology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhuo","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Urology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3471-6221","authenticated-orcid":false,"given":"Fan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Urology Renmin Hospital of Wuhan University  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214257"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175730"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab002"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.100962"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.315739.118"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-10-810895"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.140541"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2025.119963"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04654-7"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-52397-6"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1515\/biol-2022-1001"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2025.05.003"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.01.015"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-022-06635-y"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.7248"},{"issue":"3","key":"e_1_2_12_17_1","first-page":"228","article-title":"The Risk Factors of Prostate Cancer and Its Prevention: A Literature Review","volume":"48","author":"Perdana N. 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