A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Pertega Gomes, N (Autor) Outra; Felisbino, S (Autor) Outra; Massie, CE (Autor) Outra; Vizcaino, JR (Autor) Outra; Coelho, R (Autor) Outra; Sandi, C (Autor) Outra; Simoes Sousa, S (Autor) Outra; Jurmeister, S (Autor) Outra; Ramos Montoya, A (Autor) Outra; Asim, M (Autor) Outra; Tran, M (Autor) Outra; Oliveira, E (Autor) Outra; da Cunha, AL (Autor) Outra; Maximo, V (Autor) FMUP; Baltazar, F (Autor) Outra; Neal, DE (Autor) Outra; Fryer, LGD (Autor) Outra

Revista

Título: Journal of Pathology

Vol. 236

Páginas: 517-530

ISSN: 0022-3417

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 70 Citações

Scopus - 72 Citações

Outras Informações

ID Authenticus: P-00G-EGT

DOI: 10.1002/path.4547

Abstract (EN): 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. (c) 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14