[en] Methylglyoxal is a highly reactive compound derived from glycolysis. It can interact with several biological molecules like DNA, lipids or proteins leading to Advanced Glycation Product (AGE). Stress due to MG is known as a cause of several disease. It exists diverse defence mechanisms to regulate dicarbonyl stress and one of the most important is the Glyoxalase system composed of Glo1 and Glo2 enzymes.
Epigenetic disorders are correlated with many human diseases including carcinogenesis. Aberrant DNA methylation or demethylation has been recognized as common molecular alterations in human neoplasia.
To better understand the connexion between epigenetic disorders, metastatic properties and MG dicarbonyl stress in breast cancer, we used MDA-MB-231 cell line stably depleted for Glo1 to create an endogenous MG stress model.
In this in vitro model, we observed the presence of a pro-metastatic signature under MG stress and a hypermethylation of the genome that was correlated with an increase of a de novo DNA methyltransferase (DNMT3A) protein expression. Interestingly, we could reverse DNMT3A over-expression via the use of MG scavengers like carnosine.
As a perspective, we consider to investigate the MG stress-induce migratory capacities through the inhibition of DNMTs.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Tiamiou, Assia ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Dube, Gaurav; Université Libre de Bruxelles - ULB
Bizet, Martin; Université Libre de Bruxelles - ULB
