Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer

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 biogene...

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Autores principales:	Junguee Lee, Ki Cheol Park, Hae Joung Sul, Hyun Jung Hong, Kun-Ho Kim, Jukka Kero, Minho Shong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7690e024f6ab4de3af52ee9ea641e697
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spelling	oai:doaj.org-article:7690e024f6ab4de3af52ee9ea641e6972021-12-02T10:54:15ZLoss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer10.1038/s41598-021-83418-32045-2322https://doaj.org/article/7690e024f6ab4de3af52ee9ea641e6972021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83418-3https://doaj.org/toc/2045-2322Abstract 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;Ift88 flox/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.Junguee LeeKi Cheol ParkHae Joung SulHyun Jung HongKun-Ho KimJukka KeroMinho ShongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Junguee Lee Ki Cheol Park Hae Joung Sul Hyun Jung Hong Kun-Ho Kim Jukka Kero Minho Shong Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
description	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;Ift88 flox/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.
format	article
author	Junguee Lee Ki Cheol Park Hae Joung Sul Hyun Jung Hong Kun-Ho Kim Jukka Kero Minho Shong
author_facet	Junguee Lee Ki Cheol Park Hae Joung Sul Hyun Jung Hong Kun-Ho Kim Jukka Kero Minho Shong
author_sort	Junguee Lee
title	Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
title_short	Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
title_full	Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
title_fullStr	Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
title_full_unstemmed	Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
title_sort	loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7690e024f6ab4de3af52ee9ea641e697
work_keys_str_mv	AT jungueelee lossofprimaryciliapromotesmitochondriadependentapoptosisinthyroidcancer AT kicheolpark lossofprimaryciliapromotesmitochondriadependentapoptosisinthyroidcancer AT haejoungsul lossofprimaryciliapromotesmitochondriadependentapoptosisinthyroidcancer AT hyunjunghong lossofprimaryciliapromotesmitochondriadependentapoptosisinthyroidcancer AT kunhokim lossofprimaryciliapromotesmitochondriadependentapoptosisinthyroidcancer AT jukkakero lossofprimaryciliapromotesmitochondriadependentapoptosisinthyroidcancer AT minhoshong lossofprimaryciliapromotesmitochondriadependentapoptosisinthyroidcancer
_version_	1718396475985100800

Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer

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