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Publication : Primary cilia control translation and the cell cycle in medulloblastoma.

First Author  Youn YH Year  2022
Journal  Genes Dev Volume  36
Issue  11-12 Pages  737-751
PubMed ID  35798383 Mgi Jnum  J:327240
Mgi Id  MGI:7329721 Doi  10.1101/gad.349596.122
Citation  Youn YH, et al. (2022) Primary cilia control translation and the cell cycle in medulloblastoma. Genes Dev 36(11-12):737-751
abstractText  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 beta-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.
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