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http://dx.doi.org/10.14348/molcells.2018.0430

Loss of Primary Cilia Results in the Development of Cancer in the Murine Thyroid Gland  

Lee, Junguee (Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Yi, Shinae (Research Center for Endocrine and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine)
Chang, Joon Young (Research Center for Endocrine and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine)
Kim, Jung Tae (Research Center for Endocrine and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine)
Sul, Hae Joung (Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Park, Ki Cheol (Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
Zhu, Xuguang (Laboratory of Molecular Biology, National Cancer Institute)
Cheng, Sheue-yann (Laboratory of Molecular Biology, National Cancer Institute)
Kero, Jukka (Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku)
Kim, Joon (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology)
Shong, Minho (Research Center for Endocrine and Metabolic Diseases, Division of Endocrinology, Department of Internal Medicine, Chungnam National University School of Medicine)
Publication Information
Molecules and Cells / v.42, no.2, 2019 , pp. 113-122 More about this Journal
Abstract
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.
Keywords
defective ciliogenesis; dilated and destroyed thyroid follicle; malignant transformation; primary cilia;
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