期刊
CANCER CELL
卷 26, 期 6, 页码 797-812出版社
CELL PRESS
DOI: 10.1016/j.ccell.2014.10.021
关键词
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资金
- Belgian Fonds de la Recherche Scientifique (FNRS)
- Belgian Queen Elizabeth Medical Foundation
- Interuniversity Attraction Poles Program (IUAP)
- WELBIO Program of the Walloon Region
- Fondation de Spoelbergh
- Fondation ULB
Disrupted differentiation during development can lead to oncogenesis, but the underlying mechanisms remain poorly understood. Here we identify BCL6, a transcriptional repressor and lymphoma oncoprotein, as a pivotal factor required for neurogenesis and tumor suppression of medulloblastoma (MB). BCL6 is necessary for and capable of preventing the development of GNP-derived MB in mice, and can block the growth of human MB cells in vitro. BCL6 neurogenic and oncosuppressor effects rely on direct transcriptional repression of Gli1 and Gli2 effectors of the SHH pathway, through recruitment of BCOR corepressor and SIRT1 deacetylase. Our findings identify the BCL6/BCOR/SIRT1 complex as a potent repressor of the SHH pathway in normal and oncogenic neural development, with direct diagnostic and/or therapeutic relevance for SHH MB.
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