| Literature DB >> 28648376 |
Yannick D Benoit1, Ryan R Mitchell1, Ruth M Risueño1, Luca Orlando1, Borko Tanasijevic1, Allison L Boyd1, Lili Aslostovar2, Kyle R Salci3, Zoya Shapovalova1, Jennifer Russell1, Masakatsu Eguchi4, Diana Golubeva3, Monica Graham1, Anargyros Xenocostas5, Michael R Trus6, Ronan Foley6, Brian Leber6, Tony J Collins1, Mickie Bhatia7.
Abstract
Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/β-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs. Disruption of CBP-β-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction. Our study identifies Sam68 as a regulator of human CSC vulnerability. CrownEntities:
Keywords: CBP; SUMOylation; Sam68; Wnt/β-catenin; cancer stem cells; differentiation; drug; leukemia; selectivity
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Year: 2017 PMID： 28648376 DOI： 10.1016/j.chembiol.2017.05.026
Source DB: PubMed Journal: Cell Chem Biol ISSN： 2451-9448 Impact factor: 8.116