Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer.

[en] Cancer cells generally rely on aerobic glycolysis as a major source of energy. Methylglyoxal (MG), a dicarbonyl compound that is produced as a side product during glycolysis, is highly reactive and induces the formation of advanced glycation end-products that are implicated in several pathologies including cancer. All mammalian cells have an enzymatic defense against MG composed by glyoxalases GLO1 and GLO2 that converts MG to d-lactate. Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality. In this study, we used immunohistochemistry to examine the level of MG protein adducts, in a series of 102 CRC human tumors divided into four clinical stages. We consistently detected a high level of MG adducts and low GLO1 activity in high stage tumors compared to low stage ones suggesting a pro-tumor role for dicarbonyl stress. Accordingly, GLO1 depletion in CRC cells promoted tumor growth in vivo that was efficiently reversed using carnosine, a potent MG scavenger. Our study represents the first demonstration that MG adducts accumulation is a consistent feature of high stage CRC tumors. Our data point to MG production and detoxification levels as an important molecular link between exacerbated glycolytic activity and CRC progression.

Disciplines :

Oncology

Author, co-author :

Chiavarina, Barbara ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Nokin, Marie-Julie ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Bellier, Justine ; Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases

Durieux, Florence ; Université de Liège - ULiège > Form. doc. sc. bioméd. & pharma.

BLETARD, Noëlla ; Centre Hospitalier Universitaire de Liège - CHU > Service d'anatomie et cytologie pathologiques

Sherer, Felicie

LOVINFOSSE, Pierre

Peulen, Olivier ; Université de Liège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques

Verset, Laurine

Dehon, Romain

More authors (8 more)

Language :

English

Title :

Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer.

Publication date :

2017

Journal title :

International Journal of Molecular Sciences

ISSN :

1661-6596

eISSN :

1422-0067

Publisher :

Multidisciplinary Digital Publishing Institute (MDPI), Switzerland

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 15 February 2017

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