Oncotarget

Research Papers:

NF-Y activates genes of metabolic pathways altered in cancer cells

Paolo Benatti, Maria Luisa Chiaramonte, Mariangela Lorenzo, John A. Hartley, Daniel Hochhauser, Nerina Gnesutta, Roberto Mantovani, Carol Imbriano and Diletta Dolfini _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:1633-1650. https://doi.org/10.18632/oncotarget.6453

Metrics: PDF 1040 views  |   HTML 1407 views  |   ?  


Abstract

Paolo Benatti1, Maria Luisa Chiaramonte2, Mariangela Lorenzo2, John A. Hartley3, Daniel Hochhauser3, Nerina Gnesutta2, Roberto Mantovani2, Carol Imbriano1 and Diletta Dolfini2

1 Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Modena, Italy

2 Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy

3 Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, Paul O’Gorman Building, University College London, London, UK

Correspondence to:

Diletta Dolfini, email:

Keywords: transcription, cancer metabolism, NF-Y, glycolysis, SOCG pathway

Received: July 14, 2015 Accepted: November 15, 2015 Published: December 03, 2015

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 6453