KY1022, a small molecule destabilizing Ras via targeting the Wnt/ß-catenin pathway, inhibits development of metastatic colorectal cancer.
Oncotarget
; 7(49): 81727-81740, 2016 Dec 06.
Article
em En
| MEDLINE
| ID: mdl-27835580
ABSTRACT
APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis. In addition, both ß-catenin and Ras levels are highly increased in CRC, especially in metastatic CRC (mCRC). Therefore, targeting both the Wnt/ß-catenin and Ras pathways could be an ideal therapeutic approach for treating mCRC patients. In this study, we characterized the roles of KY1022, a small molecule that destabilizes both ß-catenin and Ras via targeting the Wnt/ß-catenin pathway, in inhibiting the cellular events, including EMT, an initial process of metastasis, and apoptosis. As shown by in vitro and in vivo studies using APCMin/+/K-RasG12DLA2 mice, KY1022 effectively suppressed the development of mCRC at an early stage of tumorigenesis. A small molecular approach degrading both ß-catenin and Ras via inhibition of the Wnt/ß-catenin signaling would be an ideal strategy for treatment of mCRC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tioidantoínas
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Neoplasias Colorretais
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Adenocarcinoma
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Movimento Celular
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Proteínas Proto-Oncogênicas p21(ras)
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Beta Catenina
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Via de Sinalização Wnt
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article