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Sensitisation of Cancer Cells to MLN8237, an Aurora-A Inhibitor, by YAP/TAZ Inactivation.
Oku, Yusuke; Nishiya, Naoyuki; Sugiyama, Shuhei; Sato, Haruka; Uehara, Yoshimasa.
Afiliación
  • Oku Y; Department of Integrated Information for Pharmaceutical Sciences, Iwate Medical University School of Pharmacy, Morioka, Japan yoku@iwate-med.ac.jp.
  • Nishiya N; Department of Integrated Information for Pharmaceutical Sciences, Iwate Medical University School of Pharmacy, Morioka, Japan.
  • Sugiyama S; Department of Integrated Information for Pharmaceutical Sciences, Iwate Medical University School of Pharmacy, Morioka, Japan.
  • Sato H; Department of Integrated Information for Pharmaceutical Sciences, Iwate Medical University School of Pharmacy, Morioka, Japan.
  • Uehara Y; Department of Integrated Information for Pharmaceutical Sciences, Iwate Medical University School of Pharmacy, Morioka, Japan.
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.
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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

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