title: Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer.
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.
authors: Genetics Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors: Li-Jun
authors: LJ
authors: Di
authors: Jung S
authors: JS
authors: Byun
authors: Madeline M
authors: MM
authors: Wong
authors: Clay
authors: C
authors: Wakano
authors: Tara
authors: T
authors: Taylor
authors: Sven
authors: S
authors: Bilke
authors: Songjoon
authors: S
authors: Baek
authors: Kent
authors: K
authors: Hunter
authors: Howard
authors: H
authors: Yang
authors: Maxwell
authors: M
authors: Lee
authors: Cecilia
authors: C
authors: Zvosec
authors: Galina
authors: G
authors: Khramtsova
authors: Fan
authors: F
authors: Cheng
authors: Charles M
authors: CM
authors: Perou
authors: C Ryan
authors: CR
authors: Miller
authors: Rachel
authors: R
authors: Raab
authors: Olufunmilayo I
authors: OI
authors: Olopade
authors: Kevin
authors: K
authors: Gardner
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D031204:Caloric Restriction; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D016000:Cluster Analysis; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D042822:Genomic Instability / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D054852:Small Molecule Libraries / Q000494:pharmacology; D016019:Survival Analysis; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D054852:Small Molecule Libraries; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein; D005947:Glucose
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