{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:09:12Z","timestamp":1793311752238,"version":"4.5.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>ADAMTS2, a secreted metalloproteinase essential for collagen maturation, exhibits context-dependent roles in cancer but remains uncharacterized in prostate cancer (PCa). Its potential involvement in PCa progression and underlying mechanisms are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We integrated bioinformatic analysis of TCGA-PRAD data with clinical specimen validation,\n                      <jats:italic>in vitro<\/jats:italic>\n                      functional assays (proliferation, migration, invasion), co-immunoprecipitation (Co-IP), ferroptosis sensitivity testing, pharmacological inhibition, and\n                      <jats:italic>in vivo<\/jats:italic>\n                      xenograft models to investigate ADAMTS2\u2019s expression, function, and molecular mechanisms in PCa.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ADAMTS2 was significantly upregulated in PCa tissues and cell lines, correlating with aggressive clinicopathological features and poor progression-free survival. Functionally, ADAMTS2 promoted PCa cell aggressiveness\n                      <jats:italic>in vitro<\/jats:italic>\n                      and tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Mechanistically, ADAMTS2 directly interacted with and upregulated COL1A1, leading to stimulation of the FAK\/PI3K\/AKT pathway. This cascade, in turn, enhanced the expression of ferroptosis defense proteins (SLC7A11 and GPX4), suppressed lipid peroxidation, and conferred resistance to ferroptosis. Pharmacological inhibition of FAK reversed both the oncogenic and anti-ferroptotic effects of ADAMTS2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our investigation considers ADAMTS2 as a novel oncogenic driver in PCa that promotes tumor progression by reinforcing a tumor-permissive extracellular matrix through upregulation of COL1A1 and by stimulating the FAK\/PI3K\/AKT pathway to suppress ferroptosis. These findings position ADAMTS2 as a potential predictive biomarker and a valuable therapeutic target for defeating ferroptosis resistance in PCa.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1784882","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:27:57Z","timestamp":1777264077000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["ADAMTS2 drives prostate cancer progression by activating FAK\/PI3K\/AKT signaling and suppressing ferroptosis via COL1A1"],"prefix":"10.3389","volume":"16","author":[{"given":"Jinzhuo","family":"Ning","sequence":"first","affiliation":[{"name":"Department of Urology, Renmin Hospital of Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Renmin Hospital of Wuhan 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