Sensitisation of Cancer Cells to MLN8237, an Aurora-A Inhibitor, by YAP/TAZ Inactivation.
Anticancer Res
; 38(6): 3471-3476, 2018 Jun.
Article
en En
| MEDLINE
| ID: mdl-29848699
BACKGROUND: Transcriptional co-activators YES-associated protein (YAP) and transcriptional coactivator with PDZ-motif (TAZ) stimulate the expression of cell cycle-related genes to permit for tumour cell growth. MLN8237 is a potent aurora-A kinase inhibitor; however, patients responding to MLN8237 are limited. Therefore, rational combination therapy could enhance their response. MATERIALS AND METHODS: YAP and TAZ were depleted using siRNA and then treated with MLN8237 in YAP/TAZ-dependent OVCAR-8 and MDA-MB-231 cell lines. MLN8237 was combined with fluvastatin, an agent constraining nuclear localisation of YAP/TAZ for potential combination therapy in vitro. RESULTS: Depletion of either YAP or TAZ sensitised these cell lines to MLN8237, resulting in apoptosis and reduction in aurora-A. MLN8237 reduced YAP/TAZ expression. A combination of MLN8237 with fluvastatin effectively reduced the cell viability of OVCAR-8 and MDA-MB-231 cell lines. CONCLUSION: A combination of MLN8237 and small-molecule agents inactivating YAP/TAZ, such as statins, could be a novel therapeutic strategy for YAP/TAZ-dependent cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Pirimidinas
/
Azepinas
/
Péptidos y Proteínas de Señalización Intracelular
/
Proteínas Adaptadoras Transductoras de Señales
/
Aurora Quinasa A
Límite:
Humans
Idioma:
En
Revista:
Anticancer Res
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Grecia