提高的PDLIM3表达水平在髓母细胞瘤（MB）的声波刺猬（SHH）组中经常被检测到。然而，PDLIM3在MB肿瘤发生中的可能作用仍未知。在这里，我们发现PDLIM3表达对于MB细胞中的刺猬（Hh）通路激活是必要的。PDLIM3存在于MB细胞和成纤维细胞的原始纤毛中，这种纤毛定位是通过PDLIM3蛋白的PDZ结构域介导的。删除PDLIM3可显著破坏纤毛形成并干扰MB细胞的Hh信号传导，表明PDLIM3通过支持纤毛发生促进Hh信号传导。PDLIM3蛋白物理相互作用于胆固醇，这是纤毛形成和刺猬信号传导的关键分子。在PDLIM3零细胞或成纤维细胞中，纤毛形成和Hh信号传导的破坏被外源性胆固醇治疗显著恢复，表明PDLIM3通过供应胆固醇促进纤毛发生。最后，在MB细胞中删除PDLIM3显着抑制了它们的增殖并压制了肿瘤生长，表明PDLIM3对于MB肿瘤发生是必要的。我们的研究阐明了PDLIM3在SHH-MB细胞中纤毛形成和Hh信号传导中的重要功能，支持利用PDLIM3作为定义SHH组MB的分子标记。©2023年作者，ADMCAssociazioneDifferenziamentoeMorteCellulare独家许可。

Elevated levels of PDLIM3 expression are frequently detected in sonic hedgehog (SHH) group of medulloblastoma (MB). However, the possible role of PDLIM3 in MB tumorigenesis is still unknown. Here, we found that PDLIM3 expression is necessary for hedgehog (Hh) pathway activation in MB cells. PDLIM3 is present in primary cilia of MB cells and fibroblasts, and such cilia localization is mediated by the PDZ domain of PDLIM3 protein. Deletion of PDLIM3 significantly compromised cilia formation and interfered the Hh signaling transduction in MB cells, suggesting that PDLIM3 promotes the Hh signaling through supporting the ciliogenesis. PDLIM3 protein physically interacts with cholesterol, a critical molecule for cilia formation and hedgehog signaling. The disruption of cilia formation and Hh signaling in PDLIM3 null MB cells or fibroblasts, was significantly rescued by treatment with exogenous cholesterol, demonstrating that PDLIM3 facilitates the ciliogenesis through cholesterol provision. Finally, deletion of PDLIM3 in MB cells significantly inhibited their proliferation and repressed tumor growth, suggesting that PDLIM3 is necessary for MB tumorigenesis. Our studies elucidate the critical functions of PDLIM3 in the ciliogenesis and Hh signaling transduction in SHH-MB cells, supporting to utilize PDLIM3 as a molecular marker for defining SHH group of MB in clinics.© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.