{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:43:25Z","timestamp":1777398205891,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Provincial Key Research and Development Program","award":["2025BCB090"],"award-info":[{"award-number":["2025BCB090"]}]},{"name":"Hubei Provincial Key Research and Development Program","award":["2024BCB012"],"award-info":[{"award-number":["2024BCB012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Cytokine-like receptor family 1 (CRLF1) has been implicated in tumor progression, yet its prognostic function and mechanistic actions in prostate cancer (PCa) remain elusive. Objective: This investigation sought to clarify the functional role, molecular mechanisms, and clinical relevance of CRLF1 in the progression of PCa. Methods: We conducted extensive bioinformatics analyses utilizing the protein interaction networks and the TCGA-PRAD dataset. CRLF1 and cartilage oligomeric matrix protein (COMP) expression were validated in clinical samples by qRT-PCR and Western blot (WB). Functional assessments, including Transwell invasion, flow cytometry, CCK-8, and wound healing, were conducted in vitro. An in vivo xenograft tumor model was used for further validation. Mechanistic investigations involved genetic perturbation (overexpression and inhibition) of CRLF1 and COMP. Results: Compared to benign tissues, the levels of CRLF1 and COMP were markedly elevated in PCa tissues. Bioinformatics assessments illustrated a robust positive relationship between CRLF1 and COMP, suggesting COMP may function as a downstream mediator. In vitro and in vivo investigations illustrated that silencing CRLF1 significantly suppressed PCa cell growth, invasion, and tumor progression, while enhancing apoptosis. Importantly, suppressing COMP counteracted the cancer-promoting effects triggered by CRLF1 overexpression. At the mechanistic level, CRLF1 facilitates tumor progression by modulating COMP to activate the FAK\/PI3K\/AKT signaling cascade. Conclusions: Our outcomes demonstrate that CRLF1 promotes PCa progression by targeting COMP to stimulate the FAK\/PI3K\/AKT signaling axis. This newly identified CRLF1\/COMP\/FAK\/PI3K\/AKT pathway underscores CRLF1 as a potential biomarker and therapeutic target for PCa.<\/jats:p>","DOI":"10.3390\/cancers18091395","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:55:39Z","timestamp":1777370139000},"page":"1395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CRLF1 Drives Prostate Cancer Progression via COMP-Mediated Activation of the FAK\/PI3K\/AKT Signaling Pathway"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2393-1883","authenticated-orcid":false,"given":"Zhongze","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinrun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizhe","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4919-091X","authenticated-orcid":false,"given":"Jinzhuo","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1001\/jama.2025.0228","article-title":"Prostate cancer: A review","volume":"333","author":"Raychaudhuri","year":"2025","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.eururo.2023.04.021","article-title":"2022 update on prostate cancer epidemiology and risk factors-a systematic review","volume":"84","author":"Bergengren","year":"2023","journal-title":"Eur. 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