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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.

Original publication

DOI

10.1002/path.4547

Type

Journal article

Journal

J Pathol

Publication Date

08/2015

Volume

236

Pages

517 - 530

Keywords

cell metabolism, metabolic targets, monocarboxylate transporters, poor prognosis markers, prostate cancer, Animals, Antineoplastic Agents, Cell Line, Tumor, Cell Proliferation, Disease Progression, Drug Design, Gene Expression Regulation, Neoplastic, Glycolysis, Humans, Lactic Acid, Male, Mice, Transgenic, Molecular Targeted Therapy, Monocarboxylic Acid Transporters, Neoplasm Staging, Phenotype, Prostatic Neoplasms, RNA Interference, Time Factors, Transfection, Tumor Burden