Abstract

The primary cilium is well-preserved in human differentiated thyroid cancers such as papillary and follicular carcinoma. Specific thyroid cancers such as Hürthle cell carcinoma, oncocytic variant of papillary thyroid carcinoma (PTC), and PTC with Hashimoto’s 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. Tg-Cre;Ift88flox/flox mice (in which thyroid follicles lacked primary cilia) showed irregularly dilated follicles and increased apoptosis of thyrocytes. Defective ciliogenesis caused by deleting the IFT88 and KIF3A 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.

Details

Title
Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
Author
Lee, Junguee 1 ; Park, Ki Cheol 2 ; Sul Hae Joung 1 ; Jung, Hong Hyun 3 ; Kun-Ho, Kim 4 ; Kero Jukka 5 ; Shong Minho 6 

 The Catholic University of Korea, Department of Pathology, Daejeon St. Mary’s Hospital, College of Medicine, Seoul, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224) 
 The Catholic University of Korea, Clinical Research Institute, Daejeon St. Mary’s Hospital, College of Medicine, Daejeon, Republic of Korea (GRID:grid.411947.e) (ISNI:0000 0004 0470 4224) 
 Chungnam National University School of Medicine, Research Center for Endocrine and Metabolic Diseases, Daejeon, Republic of Korea (GRID:grid.254230.2) (ISNI:0000 0001 0722 6377) 
 Chungnam National University Hospital and College of Medicine, Department of Nuclear Medicine, Daejeon, Republic of Korea (GRID:grid.411665.1) (ISNI:0000 0004 0647 2279) 
 University of Turku, Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371) 
 Chungnam National University School of Medicine, Department of Internal Medicine, Daejeon, Republic of Korea (GRID:grid.254230.2) (ISNI:0000 0001 0722 6377) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2490848882
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.