Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer.
Mol Syst Biol
; 10: 728, 2014 May 05.
Article
em En
| MEDLINE
| ID: mdl-24799285
ABSTRACT
Glutamine can play a critical role in cellular growth in multiple cancers. Glutamine-addicted cancer cells are dependent on glutamine for viability, and their metabolism is reprogrammed for glutamine utilization through the tricarboxylic acid (TCA) cycle. Here, we have uncovered a missing link between cancer invasiveness and glutamine dependence. Using isotope tracer and bioenergetic analysis, we found that low-invasive ovarian cancer (OVCA) cells are glutamine independent, whereas high-invasive OVCA cells are markedly glutamine dependent. Consistent with our findings, OVCA patients' microarray data suggest that glutaminolysis correlates with poor survival. Notably, the ratio of gene expression associated with glutamine anabolism versus catabolism has emerged as a novel biomarker for patient prognosis. Significantly, we found that glutamine regulates the activation of STAT3, a mediator of signaling pathways which regulates cancer hallmarks in invasive OVCA cells. Our findings suggest that a combined approach of targeting high-invasive OVCA cells by blocking glutamine's entry into the TCA cycle, along with targeting low-invasive OVCA cells by inhibiting glutamine synthesis and STAT3 may lead to potential therapeutic approaches for treating OVCAs.
Texto completo:
1
Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Terapias_energeticas
/
Bioenergetica
Assunto principal:
Neoplasias Ovarianas
/
Proliferação de Células
/
Metabolismo Energético
/
Glutamina
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Mol Syst Biol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos