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

Autor(es):Mostrar menos -

Pertega-Gomes, Nelma ^[1] ; Felisbino, Sergio ^[2] ; Massie, Charlie E. ^[1] ; Vizcaino, Jose R. ^[3] ; Coelho, Ricardo ^[4] ; Sandi, Chiranjeevi ^[1] ; Simoes-Sousa, Susana ^{[5, 6]} ; Jurmeister, Sarah ^[1] ; Ramos-Montoya, Antonio ^[1] ; Asim, Mohammad ^[1] ; Tran, Maxine ^[1] ; Oliveira, Elsa ^[7] ; da Cunha, Alexandre Lobo ^[7] ; Maximo, Valdemar ^{[4, 8]} ; Baltazar, Fatima ^{[5, 6]} ; Neal, David E. ^{[1, 9, 10]} ; Fryer, Lee G. D. ^[1]

Afiliação do(s) autor(es)

^[1] Canc Res UK CRUK, Cambridge Inst, Uro Oncol Res Grp, Cambridge - England

^[2] Sao Paulo State Univ UNESP, Inst Biosci, Dept Morphol, Botucatu, SP - Brazil

^[3] Ctr Hosp Porto, Dept Pathol, Oporto - Portugal

^[4] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Oporto - Portugal

^[5] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[6] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[7] Univ Porto, Inst Biomed Sci Abel Salazar ICBAS, Cell Biol Lab, P-4100 Oporto - Portugal

^[8] Univ Porto, Fac Med, Dept Pathol & Oncol, P-4100 Oporto - Portugal

^[9] Univ Cambridge, Dept Urol, Cambridge - England

^[10] Addenbrookes Hosp, Dept Oncol, S4, Cambridge - England

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PATHOLOGY; v. 236, n. 4, p. 517-530, AUG 2015.
• Citações Web of Science: 34

Resumo

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. (AU)

• Processo FAPESP: 13/08830-2 - Progressão e metástase do câncer de próstata em camundongos deficientes em PTEN (PtenloxP/loxP;PB-Cre4) ou em pRb e p53 (pRbloxP/loxP p53loxP/loxP;PB-Cre4) no epitélio prostático: marcadores de proliferação e estresse oxidativo
• Beneficiário: Sérgio Luis Felisbino
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/06802-1 - Progressão e metástase do câncer de próstata em camundongos deficientes em PTEN-/- ou em pRb-/-p53-/- no epitélio prostático (Cre/LoxP): marcadores de proliferação e estresse oxidativo
• Beneficiário: Sérgio Luis Felisbino
• Modalidade de apoio: Bolsas no Exterior - Pesquisa