The KISS1 metastasis suppressor appears to reverse the Warburg effect by shifting from glycolysis to mitochondrial beta-oxidation.
J Mol Med (Berl)
; 95(9): 951-963, 2017 Sep.
Article
en En
| MEDLINE
| ID: mdl-28597070
ABSTRACT
The shift by cancer cells toward aerobic glycolysis (Warburg effect) confers selective advantages by utilizing nutrients (e.g., lipids, amino acids, and nucleotides) to build biomass. Lipogenesis is generally enhanced, and its inhibition diminishes proliferation and survival. Re-expression of the metastasis suppressor KISS1 in human melanoma cells results in greater mitochondrial biogenesis, inhibition of glycolysis, utilization of beta-oxidation to provide energy, elevated oxidation of exogenous fatty acids, and increased expression of early-phase lipogenesis genes at both mRNA and protein levels. Correspondingly, the energy sensor AMPKß is phosphorylated, resulting in inhibitory phosphorylation of acetyl-CoA carboxylase (ACC), which is linked to enhanced beta-oxidation. Furthermore, PGC1α is required for KISS1-mediated phosphorylation of ACC and metastasis suppression. Collectively, these data further support the linkages between macromolecular metabolism and metastasis. KEY MESSAGES ⢠KISS1 alters fatty acid metabolism. ⢠There may be connections between metastasis and metabolism. ⢠PGC1alpha appears to be downstream mediator of KISS1 metastasis suppression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxidación-Reducción
/
Kisspeptinas
/
Glucólisis
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
J Mol Med (Berl)
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos