McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4L8, Canada.
McMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1280 Main Street West, MDCL 5029, Hamilton, ON L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada.
Cell Chem Biol. 2017 Jul 20;24(7):833-844.e9. doi: 10.1016/j.chembiol.2017.05.026. Epub 2017 Jun 22.
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.
靶向人类癌症干细胞（CSCs）需要识别 CSCs 与健康驻留干细胞（SCs）之间特有的脆弱性。不幸的是，支持转化 CSCs 的失调途径，如 Wnt/β-catenin 信号通路，也是健康SCs 的关键调节剂。我们使用 ICG-001 和 CWP 小分子家族，揭示 Sam68 是 CSCs 中 Wnt/β-catenin 信号通路的一个以前未被重视的调节剂。通过 ICG-001/CWP 破坏 CBP-β-catenin 相互作用，在 CSCs 中形成 Sam68-CBP 复合物，改变 Wnt 信号向凋亡和分化诱导。我们的研究确定 Sam68 是人类 CSC 易感性的调节剂。
