Artículos de revistas
A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy
Fecha
2015Registro en:
The Journal Of Pathology, v. 236, n. 4, p. 517-530, 2015.
1096-9896
10.1002/path.4547
PMC4528232.pdf
25875424
PMC4528232
Autor
Cambridge Institute
Universidade Estadual Paulista (Unesp)
Centro Hospitalar do Porto
University of Porto
University of Minho
ICVS/3Bs-PT Government Associate Laboratory
University of Cambridge
Addenbrooke's Hospital
Institución
Resumen
Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors.