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• W2769472506 startingPage "120" @default.
• W2769472506 abstract "Medulloblastoma, an aggressive cancer of the cerebellum, is among the most common pediatric brain tumors. Approximately one-third of medulloblastomas are associated with misactivation of the Hedgehog (Hh) pathway. GLI family zinc finger 2 (GLI2) coordinates the Hh transcriptional program; however, the GLI2 targets that promote cancer cell proliferation are unknown. Here, we incorporated a Gli2-EGFP allele into 2 different genetic mouse models of Hh-associated medulloblastoma. Hh signaling induced GLI2 binding to the Cdk6 promoter and activated Cdk6 expression, thereby promoting uncontrolled cell proliferation. Genetic or pharmacological inhibition of CDK6 in mice repressed the growth of Hh-associated medulloblastoma and prolonged survival through inhibition of cell proliferation. In human medulloblastoma, misactivation of Hh signaling was associated with high levels of CDK6, pointing to CDK6 as a direct transcriptional target of the Hh pathway. These results suggest that CDK6 antagonists may be a promising therapeutic approach for Hh-associated medulloblastoma in humans." @default.
• W2769472506 created "2017-12-04" @default.
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• W2769472506 date "2017-11-20" @default.
• W2769472506 modified "2023-10-17" @default.
• W2769472506 title "Hedgehog signaling drives medulloblastoma growth via CDK6" @default.
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• W2769472506 doi "https://doi.org/10.1172/jci92710" @default.
• W2769472506 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5749513" @default.
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• W2769472506 hasPublicationYear "2017" @default.
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