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Prior studies demonstrated that PI3K\/Akt signaling is important in thyroid hormone receptor \u03b2<jats:sup>PV\/PV<\/jats:sup> knock-in (PV) mice that develop metastatic thyroid cancer that most closely resembles FTC. To determine the roles of Akt isoforms in this model we crossed Akt1<jats:sup>\u2212\/\u2212<\/jats:sup>, Akt2<jats:sup>\u2212\/\u2212<\/jats:sup>, and Akt3<jats:sup>\u2212\/\u2212<\/jats:sup> mice with PV mice. Over 12\u00a0months, thyroid size was reduced for the Akt null crosses (p\u2009&lt;\u20090.001). Thyroid cancer development and local invasion were delayed in only the PVPV-Akt1 knock out (KO) mice in association with increased apoptosis with no change in proliferation. Primary-cultured PVPV-Akt1KO thyrocytes uniquely displayed a reduced cell motility. In contrast, loss of any Akt isoform reduced lung metastasis while vascular invasion was reduced with Akt1 or 3 loss. Microarray of thyroid RNA displayed incomplete overlap between the Akt KO models. The most upregulated gene was the dendritic cell (DC) marker CD209a only in PVPV-Akt1KO thyroids. Immunohistochemistry demonstrated an increase in CD209a-expressing cells in the PVPV-Akt1KO thyroids. In summary, Akt isoforms exhibit common and differential functions that regulate local and metastatic progression in this model of thyroid cancer.<\/jats:p>","DOI":"10.1038\/s41598-020-75529-0","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T11:03:40Z","timestamp":1603796620000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Akt isoform-specific effects on thyroid cancer development and progression in a murine thyroid cancer model"],"prefix":"10.1038","volume":"10","author":[{"given":"Motoyasu","family":"Saji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline S.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilak","family":"Khanal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Coombes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"La Perle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheue-Yann","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N.","family":"Tsichlis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Ringel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"key":"75529_CR1","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jbior.2014.04.001","volume":"55C","author":"A Toker","year":"2014","unstructured":"Toker, A. & Marmiroli, S. 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