====== Medulloblastoma Pathogenesis ======

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
((Wang Y, Wang Y, Chen H, Liang Q. Endothelial Cells Promote Formation of Medulloblastoma Stem-Like Cells via Notch Pathway Activation. J Mol Neurosci. 2017 Oct;63(2):152-158. doi: 10.1007/s12031-017-0965-2. Epub 2017 Aug 30. PMID: 28856557.)).
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[[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
((Maurer AJ, Bonney PA, Toho LC, Glenn CA, Agarwal S, Battiste JD, Fung KM,
Sughrue ME. Tumor necrosis-initiated complement activation stimulates
proliferation of medulloblastoma cells. Inflamm Res. 2015 Jan 22. [Epub ahead of 
print] PubMed PMID: 25603857.
)).

Combined activation of the Shh/Ptc and IGF signaling pathways is an important mechanism in MB pathogenesis
((Rao G, Pedone CA, Del Valle L, Reiss K, Holland EC, Fults DW. Sonic hedgehog
and insulin-like growth factor signaling synergize to induce medulloblastoma
formation from nestin-expressing neural progenitors in mice. Oncogene. 2004 Aug
12;23(36):6156-62. PubMed PMID: 15195141.)).

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
((Fults DW. Modeling medulloblastoma with genetically engineered mice. Neurosurg
Focus. 2005 Nov 15;19(5):E7. Review. PubMed PMID: 16398471.)).

===== BMI1 in medulloblastoma =====
[[BMI1 in medulloblastoma]]