{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:34:22Z","timestamp":1773016462178,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":272,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"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":["Prostate Cancer"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Prostate cancer is the most frequently diagnosed tumor of male reproductive system. Clinically, there is a lack of effective treatment drugs for prostate cancer. Previous studies have shown that AMPK inhibitor dorsomorphin was demonstrated to have potent antitumor effects. However, the effect of dorsomorphin on prostate cancer and its molecular mechanism are still unclear. In this study, the effects of dorsomorphin on the invasion and infiltration, epithelial\u2010mesenchymal transition (EMT), and angiogenesis were investigated in two types of prostate cancer cells (DU145 and PC\u20103). In addition, nude mouse tumorigenic experiments were performed to confirm the antitumor effect of dorsomorphin. We found that dorsomorphin treatment concentration\u2010 and time\u2010dependently inhibited the invasion and infiltration of DU145 and PC\u20103\u2009cells. In addition, dorsomorphin reduced the expression levels of extracellular matrix components and angiogenesis\u2010related proteins (HIF\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    and VEGF). Further study showed that dorsomorphin inhibited matrix deposition by antagonizing the EMT. Our results from nude mouse tumorigenic experiments further demonstrated dorsomorphin\u2019s tumor\u2010growth inhibitory effect, whereas its antimetastatic potential is supported by in vitro invasion and EMT assays. Mechanistically, dorsomorphin treatment suppressed TGF\u2010\u03b21 expression and thereby inhibited the phosphorylation and nucleation of Smad2\/3 signaling, which plays a key role in the regulation of EMT. Further study showed that dorsomorphin\u2010triggered inactivation of JAK2\/STAT3 and sonic hedgehog (Shh) signaling was involved in the inhibition of TGF\u2010\u03b21\u2010mediated EMT. Interestingly, dorsomorphin inhibited the expression and nucleation of Gli1 and Gli3 but not affected the expression of Gli2. Thus, these findings reveal that the new mechanism of AMPK inhibitor dorsomorphin against prostate cancer metastasis is through synergistically antagonizing JAK2\/STAT3 and Gli2\u2010independent Shh activation.\n                  <\/jats:p>","DOI":"10.1155\/proc\/8843174","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T08:05:21Z","timestamp":1759219521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dorsomorphin Suppresses EMT to Reduce AR\u2010Negative Prostate Cancer Metastasis by Synergistically Antagonizing JAK2\/STAT3 and Gli2\u2010Independent Shh Activation"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1362-325X","authenticated-orcid":false,"given":"Dongzhang","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guantao","family":"Lou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zujian","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongliang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0314-9910","authenticated-orcid":false,"given":"Wangjian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.21101\/cejph.a6807"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2018.08.005"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24491"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.07.018"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2022.154224"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15061902"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2022.109177"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008588"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/15330338231153618"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.06.014"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15672"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14071625"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.988794"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.614244"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.176035"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2018.0235"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26723"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.174825"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.07.008"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04573-7"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-00922-9"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2022.151955"},{"key":"e_1_2_10_23_2","article-title":"AMPK is a Direct Adenylate Charge-Regulated Protein Kinase","volume":"377","author":"Hawley S. 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