A BCL6/BCOR/SIRT1 Complex Triggers Neurogenesis and Suppresses Medulloblastoma by Repressing Sonic Hedgehog Signaling

被引：84

作者：

Tiberi, Luca ^{[1
,2
]}

Bonnefont, Jerome ^{[1
,2
]}

van den Ameele, Jelle ^{[1
,2
]}

Le Bon, Serge-Daniel ^{[1
,2
]}

Herpoel, Adele ^{[1
,2
]}

Bilheu, Angeline ^{[1
,2
]}

Baron, Beverly W. ^{[3
]}

Vanderhaeghen, Pierre ^{[1
,2
,4
]}

机构：

[1] Univ Libre Bruxelles, Inst Interdisciplinary Res IRIBHM, B-1070 Brussels, Belgium

[2] Univ Libre Bruxelles, ULB Inst Neurosci UNI, B-1070 Brussels, Belgium

[3] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA

[4] Univ Libre Bruxelles, Walloon Excellence Life Sci & Biotechnol WELBIO, B-1070 Brussels, Belgium

来源：

CANCER CELL | 2014年 / 26卷 / 06期

关键词：

CENTER B-CELLS; GERMINAL-CENTER; TRANSCRIPTIONAL REPRESSION; CEREBELLAR DEVELOPMENT; BCL6; CANCER; EXPRESSION; PATHWAY; GROWTH; TUMORIGENESIS;

D O I：

10.1016/j.ccell.2014.10.021

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：797 / 812

页数：16

共 64 条

[11] The level of sonic hedgehog signaling regulates the complexity of cerebellar foliation [J].