{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:18:58Z","timestamp":1787663938522,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["82303364"],"award-info":[{"award-number":["82303364"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ40089"],"award-info":[{"award-number":["2023JJ40089"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009377","name":"Education Department of Hunan Province","doi-asserted-by":"publisher","award":["22B0895"],"award-info":[{"award-number":["22B0895"]}],"id":[{"id":"10.13039\/100009377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","award":["202202055404"],"award-info":[{"award-number":["202202055404"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The transcription factor ETV1 plays a critical oncogenic role in tumors; its function in cancer\u2010associated fibroblasts (CAFs) remains poorly understood. We identified a positive correlation between ETV1 and CAFs infiltration in TIMER2.0, and overexpressed ETV1 predicted a poor prognosis in patients from TCGA. Consistently, ETV1 positively correlated with markers of CAFs. \u03b1\u2010SMA, PDGFR\u03b2, TGF\u2010\u03b2, COL1A1, and CTGF, markers of CAFs, were downregulated in LI90 cells cocultured with ETV1 low\u2010expressed Huh7 cells, and CTGF presented the most pronounced reduction. Though no direct ETV1 binding domains were predicted in the CTGF promoter, ETV1 activates TGF\u2010\u03b2 signaling in tumor tissues from TCGA. Intriguingly, multiple SMAD4 binding domains were predicted in the promoter of CTGF. Luciferase reporter assays, ChIP\u2010PCR, and EMSA presented that SMAD4 binds specifically to the P3 domain in CTGF promoter, which activated the transcription of CTGF. Rescue experiments indicated that ETV1 induced CTGF expression for the TGF\u2010\u03b2\/SMAD4 pathway in ETV1\u2010shRNA\u2010Lv infected Huh7 cells cocultured with LI90 cells infected with SMAD4\u2010oe\u2010Lv. In humanized immune\u2010reconstituted mouse models, low expression of ETV1 inhibited tumor growth and CTGF expression. Moreover, DEN\u2010induced murine hepatocellular carcinoma tissues exhibited elevated expression of ETV1, CTGF, PCNA, and Ki67. Clinically, ETV1 was overexpressed in tumor tissues and predicted poor progression in HCC patients. Thus, our findings reveal a novel ETV1\/TGF\/\u03b2\/SMAD\u2010CTGF signaling axis within the tumor microenvironment that facilitates tumor\u2010CAFs communication, ultimately promoting aggressive HCC progression through enhanced tumor cell proliferation.<\/jats:p>","DOI":"10.1002\/cam4.72180","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:19:32Z","timestamp":1787372372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ETV<\/scp>\n                    1\/\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2\/\n                    <scp>SMAD<\/scp>\n                    4\u2010\n                    <scp>CTGF<\/scp>\n                    Axis Activated Tumor\u2010\n                    <scp>CAFs<\/scp>\n                    Crosstalk Promotes Poor Progression in Hepatocellular Carcinoma Patients"],"prefix":"10.1002","volume":"15","author":[{"given":"Tongwang","family":"Yang","sequence":"first","affiliation":[{"name":"The Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid Changsha Medical University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiang","family":"Pang","sequence":"additional","affiliation":[{"name":"The Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid Changsha Medical University  Changsha China"},{"name":"Lishui People's Hospital  Lishui Zhejiang P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Hunan Provincial College of Clinical Laboratory Changsha Medical University  Changsha P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-1851","authenticated-orcid":false,"given":"Hongde","family":"Li","sequence":"additional","affiliation":[{"name":"The Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid Changsha Medical University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.10.031"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.08.021"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.861525"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.17998\/jlc.2024.12.02"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v16.i3.353"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2021.188638"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1460282"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2024.101130"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2023.0125"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx068"},{"key":"e_1_2_10_12_1","first-page":"3083","article-title":"Function and Regulation of the PEA3 Subfamily of ETS Transcription Factors in Cancer","volume":"10","author":"Qi T.","year":"2020","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.56434\/j.arch.esp.urol.20237608.69"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.56024"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1151-y"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00048.2019"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114504"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27703"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.03.006"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30529"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.89568"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2023.11.020"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31792"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71719-y"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2012.13.5.2385"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.738534"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23095232"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-023-02733-y"},{"key":"e_1_2_10_29_1","first-page":"71","article-title":"Cancer\u2010Associated Fibroblasts: How Do They Contribute to Metastasis?","volume":"36","author":"Kwa M. Q.","year":"2019","journal-title":"Clinical & Experimental Metastasis"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111378"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2023.188901"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/goaf090"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.655152"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.03.001"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.22310"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.12.021"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72180","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.72180","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:24:41Z","timestamp":1787660681000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.72180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":35,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cam4.72180"],"URL":"https:\/\/doi.org\/10.1002\/cam4.72180","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72180"}}