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Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer
Di L.-J.1; Byun J.S.1; Wong M.M.1; Wakano C.1; Taylor T.1; Bilke S.1; Baek S.1; Hunter K.1; Yang H.1; Lee M.1; Zvosec C.3; Khramtsova G.3; Cheng F.2; Perou C.M.2; Miller C.R.2; Raab R.4; Olopade O.I.3; Gardner K.1
2013-03-11
Source PublicationNature Communications
ISSN20411723
Volume4
Abstract

The C-terminal binding protein (CtBP) is a NADH-dependent transcriptional repressor that links carbohydrate metabolism to epigenetic regulation by recruiting diverse histone-modifying complexes to chromatin. Here global profiling of CtBP in breast cancer cells reveals that it drives epithelial-to-mesenchymal transition, stem cell pathways and genome instability. CtBP expression induces mesenchymal and stem cell-like features, whereas CtBP depletion or caloric restriction reverses gene repression and increases DNA repair. Multiple members of the CtBP-targeted gene network are selectively downregulated in aggressive breast cancer subtypes. Differential expression of CtBP-targeted genes predicts poor clinical outcome in breast cancer patients, and elevated levels of CtBP in patient tumours predict shorter median survival. Finally, both CtBP promoter targeting and gene repression can be reversed by small molecule inhibition. These findings define broad roles for CtBP in breast cancer biology and suggest novel chromatin-based strategies for pharmacologic and metabolic intervention in cancer. © 2013 Macmillan Publishers Limited.

DOI10.1038/ncomms2438
URLView the original
Indexed BySCI
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000316616400025
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Cited Times [WOS]:64   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.National Cancer Institute
2.The University of North Carolina at Chapel Hill
3.University of Chicago
4.East Carolina University
Recommended Citation
GB/T 7714
Di L.-J.,Byun J.S.,Wong M.M.,et al. Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer[J]. Nature Communications,2013,4.
APA Di L.-J..,Byun J.S..,Wong M.M..,Wakano C..,Taylor T..,...&Gardner K..(2013).Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer.Nature Communications,4.
MLA Di L.-J.,et al."Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer".Nature Communications 4(2013).
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