NF-Y activates genes of metabolic pathways altered in cancer cells
- PMID: 26646448
- PMCID: PMC4811486
- DOI: 10.18632/oncotarget.6453
NF-Y activates genes of metabolic pathways altered in cancer cells
Abstract
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.
Keywords: NF-Y; SOCG pathway; cancer metabolism; glycolysis; transcription.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
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