期刊
ONCOTARGET
卷 7, 期 48, 页码 79103-79116出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12997
关键词
primary cilia; defective ciliogenesis; thyroid hurthle cell; autophagy
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2015R1C1A1A02037434]
- Catholic Medical Center Research Foundation
- NRF - Ministry of Science, ICT & Future Planning [NRF-2014M3A9D8034464]
- BK21 Plus project of the National Research Foundation of Korea
- Chungnam National University, Republic of Korea
- National Research Foundation of Korea [2014M3A9D8034464] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hurthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland. However, most Hurthle cells found in benign and malignant thyroid diseases were devoid of primary cilia. Conventional variant of papillary carcinoma (PTC) displayed longer primary cilia than those of healthy tissue, whereas both the frequency and length of primary cilia were decreased in oncocytic variant of PTC. In addition, ciliogenesis was markedly defective in primary Hurthle cell tumors, including Hurthle cell adenomas and carcinomas, which showed higher level of autophagosome biogenesis. Remarkably, inhibition of autophagosome formation by Atg5 silencing or treatment with pharmacological inhibitors of autophagosome formation restored ciliogenesis in the Hurthle cell carcinoma cell line XTC. UC1 which exhibits a high basal autophagic flux. Moreover, the inhibition of autophagy promoted the accumulation of two factors critical for ciliogenesis, IFT88 and ARL13B. These results suggest that abnormal ciliogenesis, a common feature of Hurthle cells in diseased thyroid glands, is associated with increased basal autophagy.
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