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A Small Molecule Inhibitor of the ß-Catenin-TCF4 Interaction Suppresses Colorectal Cancer Growth In Vitro and In Vivo.
Shin, Seung Ho; Lim, Do Young; Reddy, Kanamata; Malakhova, Margarita; Liu, Fangfang; Wang, Ting; Song, Mengqiu; Chen, Hanyong; Bae, Ki Beom; Ryu, Joohyun; Liu, Kangdong; Lee, Mee-Hyun; Bode, Ann M; Dong, Zigang.
Afiliação
  • Shin SH; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA; Program in Bioinformatics and Computational Biology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Lim DY; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
  • Reddy K; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
  • Malakhova M; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
  • Liu F; The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China; The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
  • Wang T; The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China.
  • Song M; The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China; The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
  • Chen H; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
  • Bae KB; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
  • Ryu J; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
  • Liu K; The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China; The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China; The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China; The Affiliat
  • Lee MH; The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China.
  • Bode AM; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA; Program in Bioinformatics and Computational Biology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Dong Z; The Hormel Institute, University of Minnesota, Austin, MN 55912, USA; Program in Bioinformatics and Computational Biology, University of Minnesota, Minneapolis, MN 55455, USA; The China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, China; The Pathophysiology Department, The School of Basic M
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Beta Catenina / Bibliotecas de Moléculas Pequenas / Fator de Transcrição 4 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: EBioMedicine Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Beta Catenina / Bibliotecas de Moléculas Pequenas / Fator de Transcrição 4 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: EBioMedicine Ano de publicação: 2017 Tipo de documento: Article