Document Detail


Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma.
MedLine Citation:
PMID:  24335960     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Neuroblastoma arises from the embryonal neural crest secondary to a block in differentiation. Long-term patient survival correlates inversely with the extent of differentiation, and treatment with retinoic acid or other pro-differentiation agents improves survival modestly. In this study, we show the histone chaperone and epigenetic regulator CHAF1A functions in maintaining the highly de-differentiated state of this aggressive malignancy. CHAF1A is a subunit of the chromatin modifier CAF1 and it regulates H3K9 tri-methylation of key target genes regulating proliferation, survival and differentiation. Elevated CHAF1A expression strongly correlated with poor prognosis. Conversely, CHAF1A loss-of-function was sufficient to drive neuronal differentiation in vitro and in vivo. Transcriptome analysis of cells lacking CHAF1A revealed repression of oncogenic signaling pathways and a normalization of glycolytic metabolism. Our findings demonstrate that CHAF1A restricts neural crest differentiation and contributes to the pathogenesis of high-risk neuroblastoma.
Authors:
Eveline Barbieri; Katleen De Preter; Mario Capasso; Zaowen Chen; Danielle M Hsu; Gian Paolo Tonini; Steve Lefever; John Hicks; Rogier Versteeg; Andrea Pession; Frank Speleman; Eugene S Kim; Jason Matthew Shohet
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-12
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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