한빛사논문
- 조회529
Yong Ha Youn1, Shirui Hou1, Chang-Chih Wu1, Daisuke Kawauchi2, Brent A. Orr3, Giles W. Robinson4, David Finkelstein5, Makoto M. Taketo6, Richard J. Gilbertson7, Martine F. Roussel8 and Young-Goo Han1*
1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;
2Department of Biochemistry and Cellular Biology, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan;
3Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;
4Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;
5Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA;
6Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;
7Department of Oncology, Cancer Research UK Cambridge Institute, Cambridge CB2 0RE, England;
8Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
*Corresponding author.
Abstract
The primary cilium, a signaling organelle projecting from the surface of a cell, controls cellular physiology and behavior. The presence or absence of primary cilia is a distinctive feature of a given tumor type; however, whether and how the primary cilium contributes to tumorigenesis are unknown for most tumors. Medulloblastoma (MB) is a common pediatric brain cancer comprising four groups: SHH, WNT, group 3 (G3), and group 4 (G4). From 111 cases of MB, we show that primary cilia are abundant in SHH and WNT MBs but rare in G3 and G4 MBs. Using WNT and G3 MB mouse models, we show that primary cilia promote WNT MB by facilitating translation of mRNA encoding β-catenin, a major oncoprotein driving WNT MB, whereas cilium loss promotes G3 MB by disrupting cell cycle control and destabilizing the genome. Our findings reveal tumor type-specific ciliary functions and underlying molecular mechanisms. Moreover, we expand the function of primary cilia to translation control and reveal a molecular mechanism by which cilia regulate cell cycle progression, thereby providing new frameworks for studying cilium function in normal and pathologic conditions.
논문정보
- Research article
- 2022년 07월 (BRIC 등록일 2022-07-22)
- 국외 연구진
- 생명과학 > 신경생물학
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