Defective ciliogenesis in thyroid hürthle cell tumors is associated with increased autophagy
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Junguee Lee1, Shinae Yi2, Yea Eun Kang2, Joon Young Chang2, Jung Tae Kim3, Hae Joung Sul1, Jong Ok Kim1, Jin Man Kim4, Joon Kim5, Anna Maria Porcelli6, Koon Soon Kim2,3, Minho Shong2
1Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Jung-gu, Daejeon, 34943, Republic of Korea
2Research Center for Endocrine and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine, Jung-gu, Daejeon 35015, Republic of Korea
3Department of Medical Science, Chungnam National University School of Medicine, Jung-gu, Daejeon 35015, Republic of Korea
4Department of Pathology, Chungnam National University School of Medicine, Jung-gu, Daejeon 35015, Republic of Korea
5Graduate School of Medical Science and Engineering, KAIST, Yuseong-gu, Daejeon 34141, Republic of Korea
6Department of Pharmacy and Biotechnology-FABIT, University of Bologna, Bologna, Italy and Interdepartmental Industrial Research Center on Health Sciences and Technologies, University of Bologna, Bologna, Italy
Minho Shong, email: email@example.com
Keywords: primary cilia, defective ciliogenesis, thyroid hürthle cell, autophagy
Received: August 27, 2016 Accepted: October 24, 2016 Published: October 31, 2016
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, Hürthle 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 Hürthle 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 Hürthle cell tumors, including Hürthle 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 Hürthle 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 Hürthle cells in diseased thyroid glands, is associated with increased basal autophagy.
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