A Small Molecule Inhibitor of the ß-Catenin-TCF4 Interaction Suppresses Colorectal Cancer Growth In Vitro and In Vivo.
EBioMedicine
; 25: 22-31, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-29033371
ABSTRACT
Colorectal cancer is associated with aberrant activation of the Wnt pathway. ß-Catenin plays essential roles in the Wnt pathway by interacting with T-cell factor 4 (TCF4) to transcribe oncogenes. We synthesized a small molecule, referred to as HI-B1, and evaluated signaling changes and biological consequences induced by the compound. HI-B1 inhibited ß-catenin/TCF4 luciferase activity and preferentially caused apoptosis of cancer cells in which the survival is dependent on ß-catenin. The formation of the ß-catenin/TCF4 complex was disrupted by HI-B1 due to the direct interaction of HI-B1 with ß-catenin. Colon cancer patient-derived xenograft (PDX) studies showed that a tumor with higher levels of ß-catenin expression was more sensitive to HI-B1 treatment, compared to a tumor with lower expression levels of ß-catenin. The different sensitivities of PDX tumors to HI-B1 were dependent on the ß-catenin expression level and potentially could be further exploited for biomarker development and therapeutic applications against colon cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Beta Catenina
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Bibliotecas de Moléculas Pequenas
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Fator de Transcrição 4
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2017
Tipo de documento:
Article