The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells.
NF-Y activates genes of metabolic pathways altered in cancer cells / P. Benatti, M.L. Chiaramonte, M. Lorenzo, J.A. Hartley, D. Hochhauser, N. Gnesutta, R. Mantovani, C. Imbriano, D. Dolfini. - In: ONCOTARGET. - ISSN 1949-2553. - 7:2(2016 Jan 12), pp. 1633-1650.
|Titolo:||NF-Y activates genes of metabolic pathways altered in cancer cells|
CHIARAMONTE, MARIA LUISA (Secondo)
DOLFINI, DILETTA (Corresponding)
|Parole Chiave:||cancer metabolism; glycolysis; NF-Y; SOCG pathway; transcription; CCAAT-binding factor; cell line, tumor; gene expression profiling; HCT116 cells; HeLa cells; humans; immunoblotting; K562 cells; metabolic networks and pathways; models, genetic; neoplasms; oligonucleotide array sequence analysis; reverse transcriptase polymerase chain reaction; gene expression regulation, neoplastic; RNA interference; oncology|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
|Data di pubblicazione:||12-gen-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.18632/oncotarget.6453|
|Appare nelle tipologie:||01 - Articolo su periodico|