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Publication : Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma.

First Author  Badodi S Year  2017
Journal  Cell Rep Volume  21
Issue  10 Pages  2772-2784
PubMed ID  29212025 Mgi Jnum  J:265988
Mgi Id  MGI:6104215 Doi  10.1016/j.celrep.2017.11.021
Citation  Badodi S, et al. (2017) Convergence of BMI1 and CHD7 on ERK Signaling in Medulloblastoma. Cell Rep 21(10):2772-2784
abstractText  We describe molecular convergence between BMI1 and CHD7 in the initiation of medulloblastoma. Identified in a functional genomic screen in mouse models, a BMI1(High);CHD7(Low) expression signature within medulloblastoma characterizes patients with poor overall survival. We show that BMI1-mediated repression of the ERK1/2 pathway leads to increased proliferation and tumor burden in primary human MB cells and in a xenograft model, respectively. We provide evidence that repression of the ERK inhibitor DUSP4 by BMI1 is dependent on a more accessible chromatin configuration in G4 MB cells with low CHD7 expression. These findings extend current knowledge of the role of BMI1 and CHD7 in medulloblastoma pathogenesis, and they raise the possibility that pharmacological targeting of BMI1 or ERK may be particularly indicated in a subgroup of MB with low expression levels of CHD7.
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