Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer
| Autor: | Rachel Elizabeth Raab, Maxwell P. Lee, Galina Khramtsova, Tara J. Taylor, Kent W. Hunter, C. Ryan Miller, Songjoon Baek, Fan Cheng, Howard H. Yang, Olufunmilayo I. Olopade, Jung S. Byun, Kevin Gardner, Madeline M. Wong, Cecilia Zvosec, Charles M. Perou, Lijun Di, Sven Bilke, Clay Wakano |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Genome instability
Epithelial-Mesenchymal Transition DNA Repair DNA repair Cellular differentiation General Physics and Astronomy Down-Regulation Breast Neoplasms Biology General Biochemistry Genetics and Molecular Biology Article Epithelium Genomic Instability Small Molecule Libraries CTBP1 Cluster Analysis Humans Gene Regulatory Networks Neoplasm Invasiveness Epigenetics Gene Caloric Restriction Regulation of gene expression Genetics Multidisciplinary Binding Sites Genome Human Cell Differentiation Epithelial Cells General Chemistry Prognosis Survival Analysis Chromatin Up-Regulation DNA-Binding Proteins Gene Expression Regulation Neoplastic Alcohol Oxidoreductases Glucose Cancer research MCF-7 Cells Neoplastic Stem Cells Female |
| Zdroj: | Nature communications |
| DOI: | 10.17615/jzdr-pp07 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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