Sam68 Allows Selective Targeting of Human Cancer Stem Cells
Sam68 Allows Selective Targeting of Human Cancer Stem Cells
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DOI：
10.1016/j.chembiol.2017.05.026
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发表时间：
2017-07-20
影响因子：
8.6
通讯作者：
Bhatia, Mickie
中科院分区：
文献类型：
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作者：
Benoit, Yannick D.;Mitchell, Ryan R.;Bhatia, Mickie
靶向人类癌症干细胞（CSC）需要鉴定CSC相对于健康驻留干细胞（SC）的独特脆弱性。不幸的是，支持转化的CSC的失调途径，如Wnt/β-连环蛋白信号传导，也是健康SC的关键调节因子。使用ICG-001和CWP家族的小分子，我们揭示了Sam 68作为CSCs内Wnt/b-连环蛋白信号传导的先前未被认识的调节剂。通过ICG-001/CWP破坏CBP-β-连环蛋白相互作用诱导CSC中Sam 68-CBP复合物的形成，其改变Wnt信号传导朝向凋亡和分化诱导。我们的研究确定Sam 68是人类CSC脆弱性的调节因子。
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/beta-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/b-catenin signaling within CSCs. Disruption of CBP-beta-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.