{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:37:35Z","timestamp":1776926255714,"version":"3.51.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prostate cancer (PCa) is a common malignant tumor in males, and castration-resistant prostate cancer (CRPC) represents an advanced stage with limited treatment options and poor prognosis. Talin-1 (TLN1) is a cytoskeletal protein implicated in tumor progression, but its specific role and mechanism in CRPC remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mass spectrometry (MS) was used to analyze serum peptides from patients with hormone-sensitive prostate cancer (HSPC) and CRPC. TLN1 expression was further validated in clinical prostate tissue samples (59 PCa, 17 benign prostatic hyperplasia) via immunohistochemistry, qPCR, and Western blot. Functional assays (CCK-8, colony formation, wound healing, Transwell) and a nude mouse xenograft model were employed to assess the effects of TLN1 knockdown on CRPC cell lines (DU145, PC3). Transcriptome sequencing, molecular docking, and co-immunoprecipitation (Co-IP) were conducted to explore downstream mechanisms and interactions. Western blot analysis was applied to examine the impact of TLN1 knockdown on apoptosis and the PI3K-AKT, MAPK, and NF-\u03baB signaling pathways in CRPC cell lines. Rescue experiments were performed by knocking down both TLN1 and nerve growth factor receptor (NGFR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TLN1 expression was significantly upregulated in CRPC patient serum and PCa tissues. Knockdown of TLN1 inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), promoted apoptosis in CRPC cells, and suppressed tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Transcriptome analysis identified NGFR as significantly upregulated upon TLN1 knockdown. TLN1 knockdown can influence the malignant progression of CRPC through the MAPK and PI3K-AKT signaling pathways. Molecular docking and Co-IP confirmed a direct interaction between TLN1 and NGFR. Knockdown of NGFR reversed the tumor-suppressive effects induced by TLN1 silencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TLN1 inhibits the progression of CRPC by interacting with and regulating the tumor suppressor NGFR. The TLN1\/NGFR axis represents a novel potential therapeutic target for CRPC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1802129","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:38:20Z","timestamp":1776922700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TLN1 interacts with NGFR and suppresses the development of castration-resistant prostate cancer by upregulating NGFR"],"prefix":"10.3389","volume":"17","author":[{"given":"Sixin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology, Affiliated Hospital of Jiangnan University","place":["Wuxi, Jiangsu, China"]},{"name":"Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Affiliated 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