Glycant stress highlighted in breast cancer cells

In the continuity of their previous work which evidenced the role of glycation stress in cancer and metastatic progression, a new study published by the group of Dr. Akeila Bellahcène (Metastasis Research Laboratory at GIGA-Cancer, Prof. V. Castronovo and Dr. A. Bellahcène) reports an original gene expression signature related to glycation stress. This latter, although less described than oxidative stress, plays a key role in tumor cells whose preferred energy metabolic pathway is glycolysis. Indeed, it is at the fifth step of glycolysis that methylglyoxal, a reactive dicarbonyl, will form spontaneously from triose phosphates. This metabolite, that is 20 000-fold more reactive than glucose, will react with proteins, DNA and lipids to form adducts whose deleterious effects are demonstrated in complications of type 2 diabetes and in neurodegenerative diseases such as Alzheimer's disease. As far as cancer is concerned, the molecular mechanisms associated with the pro-cancer effects of methylglyoxal are still poorly understood. This study performed by Dr. Marie-Julie Nokin at the MRL and published in Breast Cancer Research has defined methylglyoxal stress as being associated with a specific metastatic gene signature revealed using high-throughput RNA sequencing. This signature recapitulates a series of genes whose expression induced major changes in the extracellular matrix (ECM), in favor of the migration and invasion of breast cancer cells. The inhibition of methylglyoxal stress is possible thanks to carnosine, a natural dipeptide, whose anti-metastatic effects have been demonstrated by the MRL.

This study opens up new research perspectives that will notably lead Dr. Bellahcene's team to study the stress of methylglyoxal in hepatocellular carcinoma which develop in the setting of ECM remodeling and fibrosis. The effect of carnosine will be evaluated using models of hepatic cancer in order to propose methylglyoxal stress blockade as a promising new anti-cancer therapy.



Methylglyoxal, a glycolysis metabolite, triggers metastasis through MEK/ERK/SMAD1 pathway activation in breast cancer.

Nokin MJ, Bellier J, Durieux F, Peulen O, Rademaker G, Gabriel M, Monseur C, Charloteaux B, Verbeke L, van Laere S, Roncarati P, Herfs M, Lambert C, Scheijen J, Schalkwijk C, Colige A, Caers J, Delvenne P, Turtoi A, Castronovo V, Bellahcène A.

Breast Cancer Research 2019, 21(1):11. doi: 10.1186/s13058-018-1095-7.

Share this news