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.

中文翻译：

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原发纤毛控制髓母细胞瘤的翻译和细胞周期


初级纤毛是从细胞表面突出的信号细胞器，控制细胞的生理和行为。初级纤毛的存在或不存在是特定肿瘤类型的显着特征；然而，对于大多数肿瘤来说，初级纤毛是否以及如何促进肿瘤发生尚不清楚。髓母细胞瘤 (MB) 是一种常见的儿童脑癌，包括四组：SHH、WNT、第 3 组 (G3) 和第 4 组 (G4)。从 111 个 MB 病例中，我们发现初级纤毛在 SHH 和 WNT MB 中丰富，但在 G3 和 G4 MB 中很少见。使用WNT和G3 MB小鼠模型，我们发现初级纤毛通过促进编码β-连环蛋白（一种驱动WNT MB的主要癌蛋白）的mRNA翻译来促进WNT MB，而纤毛损失通过破坏细胞周期控制和不稳定基因组来促进G3 MB。我们的研究结果揭示了肿瘤类型特异性的纤毛功能和潜在的分子机制。此外，我们将初级纤毛的功能扩展到翻译控制，揭示了纤毛调节细胞周期进程的分子机制，从而为研究正常和病理条件下纤毛的功能提供了新的框架。