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In our study, we sought to investigate the potential oncogenic mechanisms of the <jats:italic>PAX8\u2010GLIS3<\/jats:italic> fusion gene. Forced expression of PAX8\u2010GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy\u2010ori 3\u20101) and embryonic kidney (HEK\u2010293) cells. Moreover, in xenografts, Nthy\u2010ori 3\u20101 PAX8\u2010GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8\u2010GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the <jats:italic>PAX8<\/jats:italic>\u2010<jats:italic>GLIS3<\/jats:italic> fusion gene are, at least in part, due to an increased activation of the SHH pathway.<\/jats:p>","DOI":"10.1002\/ijc.33040","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T06:04:42Z","timestamp":1588917882000},"page":"2253-2264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Oncogenic properties and signaling basis of the <scp><i>PAX8\u2010GLIS3<\/i><\/scp> fusion gene"],"prefix":"10.1002","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-3544","authenticated-orcid":false,"given":"Thais","family":"Basili","sequence":"first","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York New York 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