Glucose metabolism and hexosamine pathway regulate oncogene-induced senescence

A Corrigendum to this article was published on 14 August 2014 6 DOI / 10.1038/cddis.2014.360Since the publication of this paper the authors have noticed an error in the abstract section. ‘Inversely, expressing a G6P,pharmacological inhibition of HK2,’ is replaced by ‘Inversely, expressing a glucose-6-phosphatase, pharmacological inhibition of HK2,’.The corrected article appears online together with this corrigendum.The authors would like to apologize for any inconvenience caused.; International audience; Oncogenic stress-induced senescence (OIS) prevents the ability of oncogenic signals to induce tumorigenesis. It is now largely admitted that the mitogenic effect of oncogenes requires metabolic adaptations to respond to new energetic and bio constituent needs. Yet, whether glucose metabolism affects OIS response is largely unknown. This is largely because of the fact that most of the OIS cellular models are cultivated in glucose excess. In this study, we used human epithelial cells, cultivated without glucose excess, to study alteration and functional role of glucose metabolism during OIS. We report a slowdown of glucose uptake and metabolism during OIS. Increasing glucose metabolism by expressing hexokinase2 (HK2), which converts glucose to glucose-6phosphate (G6P), favors escape from OIS. Inversely, expressing a glucose-6-phosphatase, pharmacological inhibition of HK2, or adding nonmetabolizable glucose induced a premature senescence. Manipulations of various metabolites covering G6P downstream pathways (hexosamine, glycolysis, and pentose phosphate pathways) suggest an unexpected role of the hexosamine pathway in controlling OIS. Altogether, our results show that decreased glucose metabolism occurs during and participates to OIS.