Aberrant FGF signaling promotes granule neuron precursor expansion in SHH subgroup infantile medulloblastoma

• DOI: 10.7554/elife.100767.1
• Publication Date: 2024-09-12T16:25:42Z
• Authors: Odessa R Yabut; Hector Gomez; Jessica Arela; Jesse Garcia Cast...; Thomas Ngo; Samuel J Pleasure
• Keywords: p53; 0301 basic medicine; QH301-705.5; Knockout; Science; medulloblastoma; neuroscience; developmental biology; Mice; 03 medical and health sciences; Neural Stem Cells; Animals; Humans; Hedgehog Proteins; human; Biology (General); Cerebellar Neoplasms; mouse; Neurons; Sufu; Q; R; Infant; Fibroblast Growth Factors; Repressor Proteins; Sonic Hedgehog; Medicine; Medulloblastoma; Signal Transduction; Developmental Biology

Mutations in Sonic Hedgehog (SHH) signaling pathway genes, e.g. Suppressor of Fused (SUFU), drive granule neuron precursors (GNP) to form medulloblastomas (MB SHH ). However, how different molecular lesions the Shh transformation is frequently unclear, and SUFU mutations cerebellum seem distinct. In this study, we show that fibroblast growth factor 5 (FGF5) integral for many infantile MB cases FGF5 expression uniquely upregulated tumors. Similarly, mice lacking (Sufu-cKO), ectopically express specifically along secondary fissure where GNPs harbor preneoplastic FGFR also activated region. Treatment with an antagonist rescues severe GNP hyperplasia restores cerebellar architecture. Thus, direct inhibition FGF may be a promising novel therapeutic candidate .