Mol. Cells 2019; 42(2): 113~122
Loss of Primary Cilia Results in the Development of Cancer in the Murine Thyroid Gland
Junguee Lee1, Shinae Yi2, Joon Young Chang2, Jung Tae Kim2, Hae Joung Sul1, Ki Cheol Park3, Xuguang Zhu4, Sheue-yann Cheng4, Jukka Kero5, Joon Kim6, and Minho Shong2,*
1Department of Pathology, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea, 2Research Center for Endocrine and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Korea, 3Clinical Research Institute, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Korea, 4Laboratory of Molecular Biology, National Cancer Institute, MD 20892-4264, USA, 5Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland, 6Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34040, Korea
Received November 21, 2018; Revised November 25, 2018; Accepted November 26, 2018.; Published online January 2, 2019.
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Communications at the interface between the apical membrane of follicular cells and the follicular lumen are critical for the homeostasis of thyroid gland. Primary cilia at the apical membrane of thyroid follicular cells may sense follicular luminal environment and regulate follicular homeostasis, although their role in vivo remains to be determined. Here, mice devoid of primary cilia were generated by thyroid follicular epithelial cell-specific deletion of the gene encoding intraflagellar transport protein 88 (Ift88 ). Thyroid follicular cellspecific Ift88-deficient mice showed normal folliculogenesis and hormonogenesis; however, those older than 7 weeks showed irregularly dilated and destroyed follicles in the thyroid gland. With increasing age, follicular cells with malignant properties showing the characteristic nuclear features of human thyroid carcinomas formed papillary and solid proliferative nodules from degenerated thyroid follicles. Furthermore, malignant tumor cells manifested as tumor emboli in thyroid vessels. These findings suggest that loss-of-function of Ift88/primary cilia results in malignant transformation from degenerated thyroid follicles.
defective ciliogenesis, dilated and destroyed thyroid follicle, malignant transformation, primary cilia

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