{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:06:16Z","timestamp":1789027576230,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteosarcoma is the most common primary malignant bone tumor and is associated with a high mortality rate due to its pronounced metastatic potential. Although tricin has been proposed as a chemosensitizer in various malignancies, its anti\u2010metastatic effect in osteosarcoma remains poorly characterized. This study investigated whether tricin suppresses metastasis in human osteosarcoma cells and explored the underlying molecular mechanisms. Our results revealed that tricin significantly inhibited the migration and invasion of U2OS and Saos\u20102 osteosarcoma cells and downregulated ZNF503 expression at both the mRNA and protein levels. Similarly, siRNA\u2010mediated knockdown of ZNF503 suppressed cell migration, as confirmed by immunofluorescence analysis. Tricin treatment also reduced phosphorylation of PI3K and Akt, without affecting the activation of ERK1\/2, JNK1\/2, or p38. Additionally, intracellular levels of PIP3 were diminished following tricin exposure. Notably, the Akt activator SC\u201079 significantly reversed tricin\u2010induced suppression of both ZNF503 expression and cell migration in U2OS and Saos\u20102 cells. In conclusion, these findings suggest that ZNF503 inhibits osteosarcoma cell motility via the PI3K\u2013PIP3\u2013Akt signaling axis and that tricin exerts anti\u2010metastatic effects by targeting this pathway. Tricin may therefore represent a promising therapeutic agent for inhibiting osteosarcoma metastasis.<\/jats:p>","DOI":"10.1002\/ddr.70374","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:21:26Z","timestamp":1787646086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tricin Inhibits Human Osteosarcoma Cell Metastasis via Suppression of ZNF503 and the PI3K\u2013PIP3\u2013Akt Pathway"],"prefix":"10.1002","volume":"87","author":[{"given":"Chia\u2010Hsuan","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Sin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-8719","authenticated-orcid":false,"given":"Pei\u2010Ni","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-1888","authenticated-orcid":false,"given":"Yi\u2010Hsien","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-8352","authenticated-orcid":false,"given":"Chih\u2010Hsin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine China Medical University Taichung Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan"},{"name":"Chinese Medicine Research Center China Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Chiu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-7927","authenticated-orcid":false,"given":"Shun\u2010Fa","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko\u2010Hsiu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"School of Medicine Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602124"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800908784293659"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy310"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020164"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9106"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7138"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21148"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.86"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl221"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arthro.2004.03.010"},{"issue":"11","key":"e_1_2_8_13_1","first-page":"1163","article-title":"Characterization of Potentially Chemopreventive Phenols in Extracts of Brown Rice That Inhibit the Growth of Human Breast and Colon Cancer Cells","volume":"9","author":"Hudson E. 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