| First Author | Shin SH | Year | 2017 |
| Journal | EBioMedicine | Volume | 25 |
| Pages | 22-31 | PubMed ID | 29033371 |
| Mgi Jnum | J:268186 | Mgi Id | MGI:6269106 |
| Doi | 10.1016/j.ebiom.2017.09.029 | Citation | Shin SH, et al. (2017) A Small Molecule Inhibitor of the beta-Catenin-TCF4 Interaction Suppresses Colorectal Cancer Growth In Vitro and In Vivo. EBioMedicine 25:22-31 |
| abstractText | Colorectal cancer is associated with aberrant activation of the Wnt pathway. beta-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 beta-catenin/TCF4 luciferase activity and preferentially caused apoptosis of cancer cells in which the survival is dependent on beta-catenin. The formation of the beta-catenin/TCF4 complex was disrupted by HI-B1 due to the direct interaction of HI-B1 with beta-catenin. Colon cancer patient-derived xenograft (PDX) studies showed that a tumor with higher levels of beta-catenin expression was more sensitive to HI-B1 treatment, compared to a tumor with lower expression levels of beta-catenin. The different sensitivities of PDX tumors to HI-B1 were dependent on the beta-catenin expression level and potentially could be further exploited for biomarker development and therapeutic applications against colon cancer. |
