Open AccessGlyoxalase 1 sustains the metastatic phenotype of prostate cancer cells via EMT control
Author(s) -
Antognelli Cinzia,
Cecchetti Rodolfo,
Riuzzi Francesca,
Peirce Matthew J.,
Talesa Vincenzo N.
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13581
Subject(s) - methylglyoxal , metastasis , cancer research , prostate cancer , epithelial–mesenchymal transition , phenotype , cancer , medicine , glycation , chemistry , biology , enzyme , biochemistry , receptor , gene
Abstract Metastasis is the primary cause of death in prostate cancer ( PC a) patients. Effective therapeutic intervention in metastatic PC a is undermined by our poor understanding of its molecular aetiology. Defining the mechanisms underlying PC a metastasis may lead to insights into how to decrease morbidity and mortality in this disease. Glyoxalase 1 (Glo1) is the detoxification enzyme of methylglyoxal ( MG ), a potent precursor of advanced glycation end products ( AGE s). Hydroimidazolone ( MG ‐H1) and argpyrimidine ( AP ) are AGE s originating from MG ‐mediated post‐translational modification of proteins at arginine residues. AP is involved in the control of epithelial to mesenchymal transition ( EMT ), a crucial determinant of cancer metastasis and invasion, whose regulation mechanisms in malignant cells are still emerging. Here, we uncover a novel mechanism linking Glo1 to the maintenance of the metastatic phenotype of PC a cells by controlling EMT by engaging the tumour suppressor miR‐101, MG ‐H1‐ AP and TGF ‐β1/Smad signalling. Moreover, circulating levels of Glo1, miR‐101, MG ‐H1‐ AP and TGF ‐β1 in patients with metastatic compared with non‐metastatic PC a support our in vitro results, demonstrating their clinical relevance. We suggest that Glo1, together with miR‐101, might be potential therapeutic targets for metastatic PC a, possibly by metformin administration.