A study revealed that Notch pathway activation played a key role in the formation of stem-like cells in MB and had valuable meaning for further investigation of targeted therapies 1).
Medulloblastoma, occurs with increased frequency in individuals with Fanconi anemia who have biallelic germline mutations in BRCA2.
Tumor necrosis-initiated complement activation stimulates proliferation of medulloblastoma cells 2).
Combined activation of the Shh/Ptc and IGF signaling pathways is an important mechanism in MB pathogenesis 3).
Both pathways are essential regulators of granule neuron precursors (GNP) proliferation during cerebellar development. In cultured GNPs, IGF signaling stabilizes the oncogenic transcription factor N-myc by inhibiting glycogen synthase kinase 3beta-dependent phosphorylation and consequent degradation of N-myc. However, determinants of Shh and IGF tumorigenicity in vivo remain unknown
Activation of the Sonic hedgehog (Shh)/Patched signaling pathway in the postnatal cerebellum is sufficient to induce medulloblastoma in mice. Activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway by insulin-like growth factor-II, inactivation of the p53 tumor suppressor protein, loss of DNA damage repair mechanisms, and ectopic expression of Myc oncoproteins cooperate with Shh/Patched signaling to enhance tumor formation in mice. Ectopic expression of alpha and beta interferons in the developing brain also induces Shh-mediated medulloblastoma formation, suggesting a possible role for antiviral response in the genesis of medulloblastoma 4).