{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T18:08:34Z","timestamp":1788718114429,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Cancer\u2010associated fibroblasts (CAFs) are key stroma cells that play dominant roles in the migration and invasion of several types of cancer through the secretion of inflammatory cytokine IL\u201017A. This study aims to identify the potential role and regulatory mechanism of CAFs\u2010secreted IL\u201017A in the migration and invasion of prostate cancer (PC). CAFs and normal fibroblasts (NFs) were obtained from fresh PC and its adjacent normal tissues, respectively. PC cells LNCaP and DU145 were co\u2010cultured with the conditioned medium from the CAFs and NFs. IL\u201017A level was determined by ELISA in the cell supernatant. CCK\u20108, wound healing, Transwell assay, western blot analysis, staining, and primary PC lung metastasis assays were employed in vivo or in vitro to explore the effect of CAFs and IL\u201017A secreted by them on proliferation, migration, invasion, epithelial\u2212mesenchymal transition (EMT) and metastasis of PC. CAFs stimulated the migration and invasion of PC cells. Importantly, CAFs exerted their roles by directly secreting IL\u201017A, leading to a significant increase in migration and invasion in PC cells. Mechanically, IL\u201017A promoted Smad3\/p38 MAPK pathway\u2010mediated EMT process, contributing to cell migration and invasion. Furthermore, CAFs secreting IL\u201017A activated the Smad3\/p38 MAPK pathway and thus facilitated tumor growth and metastasis in nude mice. This study identifies a novel signaling pathway by which CAFs mediate migration and invasion of PC via upregulation of Smad3\/p38 MAPK\u2010mediated EMT in an IL\u201017A\u2010dependent manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70047","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T05:39:53Z","timestamp":1738129193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Pro\u2010Migratory and Pro\u2010Invasive Roles of Cancer\u2010Associated Fibroblasts Secreted IL\u201017A in Prostate Cancer"],"prefix":"10.1002","volume":"39","author":[{"given":"Feng","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Urology and Andrology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuren","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology and Andrology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology and Andrology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Urology and Andrology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2078-1309","authenticated-orcid":false,"given":"Peng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Urology and Andrology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.09.007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041551"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.10.012"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124449"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-018-0004-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00546-5"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00048.2019"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01163-6"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-019-0505-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-4843"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131195"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110757"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24605"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22971"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109741"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01497-w"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216526"},{"issue":"2","key":"e_1_2_10_19_1","first-page":"1195","article-title":"Effects of miR\u2010129\u20103p on Biological Functions of Prostate Cancer Cells Through Targeted Regulation of Smad3","volume":"19","author":"Jia Y.","year":"2020","journal-title":"Oncology Letters"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12634"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010448"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.71595"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26595"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232314917"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12121900"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11243993"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-023-01828-2"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116791"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.764151"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/md21060345"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17000"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03456"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-1003-0"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000457933"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.10.015"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06007-4"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-021-03618-2"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2021.1909242"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-017-2014-7"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.12680"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-02113-5"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071887"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12050802"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.109257"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01731-z"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2024.109568"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23058"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23343"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.37455"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.03.002"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.12.001"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12121723"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.240"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112767"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124037"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.768813"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7689"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02290-0"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00080.2012"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad043"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00950-z"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.200204"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114667"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.372"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2020.108407"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70047","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70047","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70047","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:28:19Z","timestamp":1780338499000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/jbt.70047"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70047","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,29]]},"assertion":[{"value":"2024-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70047"}}