{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:23:04Z","timestamp":1789006984421,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"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":["Cancer Medicine"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy. While the prognosis of PTC is generally favorable, some cases exhibit aggressive behavior, leading to metastasis and recurrence. ASAP1 (ArfGAP with SH3, ankyrin repeats, and PH domain 1), an ADP\u2010ribosylation factor GTPase\u2010activating protein, has been implicated in tumor metastasis. However, its role in PTC remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ASAP1 expression in PTC was evaluated using TCGA and GEO databases. Studies in PTC cell lines (MDA\u2010T32 and MDA\u2010T85) included lentiviral\u2010mediated knockdown and overexpression of ASAP1 to assess effects on epithelial\u2013mesenchymal transition (EMT) marker expression, cell proliferation, and invasive capacity. TGF\u03b2 pathway activity was examined by p\u2010SMAD2 Western blotting and luciferase reporter assays. ASAP1\u2010SMAD2\/3 interactions were analyzed using co\u2010immunoprecipitation (CO\u2010IP) and immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ASAP1 was aberrantly upregulated in PTC. Lentiviral knockdown of ASAP1 in PTC cells suppressed the EMT process. Reduced ASAP1 expression also inhibited cell survival, proliferation, migration, invasion, and the expression of p\u2010SMAD2 in the TGF\u03b2 pathway in PTC cells. Conversely, ASAP1 overexpression reversed these effects. Mechanistically, ASAP1 interacts with the SMAD2\/3 complex, forming a positive feedback loop with TGF\u03b2 signaling that promotes EMT and cell invasiveness in PTC cells, which suggests its potential role in PTC metastasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that targeting ASAP1 may offer a novel therapeutic strategy to limit PTC metastasis by suppressing EMT and attenuating the TGF\u03b2 pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71075","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T12:38:48Z","timestamp":1753965528000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>ASAP1<\/scp>\n                    Promotes Epithelial to Mesenchymal Transition by Activating the\n                    <scp>TGF\u03b2<\/scp>\n                    Pathway in Papillary Thyroid Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Shiji","family":"Song","sequence":"first","affiliation":[{"name":"Department of Thyroid Surgery The First Affiliated Hospital, Zhengzhou University  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixing","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery The First Affiliated Hospital, Zhengzhou University  Zhengzhou Henan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics The Third Affiliated Hospital, Zhengzhou University  Zhengzhou Henan People's Republic of 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