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Specific thyroid cancers such as H\u00fcrthle cell carcinoma, oncocytic variant of papillary thyroid carcinoma (PTC), and PTC with Hashimoto\u2019s thyroiditis show reduced biogenesis of primary cilia; these cancers are often associated the abnormalities in mitochondrial function. Here, we examined the association between primary cilia and the mitochondria-dependent apoptosis pathway. <jats:italic>Tg-Cre;Ift88<\/jats:italic><jats:sup>flox\/flox<\/jats:sup> mice (in which thyroid follicles lacked primary cilia) showed irregularly dilated follicles and increased apoptosis of thyrocytes. Defective ciliogenesis caused by deleting the <jats:italic>IFT88<\/jats:italic> and <jats:italic>KIF3A<\/jats:italic> genes from thyroid cancer cell lines increased VDAC1 oligomerization following VDAC1 overexpression, thereby facilitating upregulation of mitochondria-dependent apoptosis. Furthermore, VDAC1 localized with the basal bodies of primary cilia in thyroid cancer cells. These results demonstrate that loss-of-function of primary cilia results in apoptogenic stimuli, which are responsible for mitochondrial-dependent apoptotic cell death in differentiated thyroid cancers. Therefore, regulating primary ciliogenesis might be a therapeutic approach to targeting differentiated thyroid cancers.<\/jats:p>","DOI":"10.1038\/s41598-021-83418-3","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T09:14:59Z","timestamp":1613812499000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer"],"prefix":"10.1038","volume":"11","author":[{"given":"Junguee","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Cheol","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Joung","family":"Sul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Jung","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Ho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Kero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minho","family":"Shong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"key":"83418_CR1","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nrm3085","volume":"12","author":"H Ishikawa","year":"2011","unstructured":"Ishikawa, H. & Marshall, W. 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