GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity.
Cell Chem Biol
; 23(5): 567-578, 2016 05 19.
Article
en En
| MEDLINE
| ID: mdl-27185638
ABSTRACT
Breast cancers possess fundamentally altered metabolism that fuels their pathogenicity. While many metabolic drivers of breast cancers have been identified, the metabolic pathways that mediate breast cancer malignancy and poor prognosis are less well understood. Here, we used a reactivity-based chemoproteomic platform to profile metabolic enzymes that are enriched in breast cancer cell types linked to poor prognosis, including triple-negative breast cancer (TNBC) cells and breast cancer cells that have undergone an epithelial-mesenchymal transition-like state of heightened malignancy. We identified glutathione S-transferase Pi 1 (GSTP1) as a novel TNBC target that controls cancer pathogenicity by regulating glycolytic and lipid metabolism, energetics, and oncogenic signaling pathways through a protein interaction that activates glyceraldehyde-3-phosphate dehydrogenase activity. We show that genetic or pharmacological inactivation of GSTP1 impairs cell survival and tumorigenesis in TNBC cells. We put forth GSTP1 inhibitors as a novel therapeutic strategy for combatting TNBCs through impairing key cancer metabolism and signaling pathways.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Triazinas
/
Gutatión-S-Transferasa pi
/
Neoplasias de la Mama Triple Negativas
/
Leucina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos