Sam68 Allows Selective Targeting of Human Cancer Stem Cells

被引：41

作者：

Benoit, Yannick D. ^{[1
]}

Mitchell, Ryan R. ^{[1
]}

Risueno, Ruth M. ^{[1
]}

Orlando, Luca ^{[1
]}

Tanasijevic, Borko ^{[1
]}

Boyd, Allison L. ^{[1
]}

Aslostovar, Lili ^{[1
,2
]}

Salci, Kyle R. ^{[2
]}

Shapovalova, Zoya ^{[1
]}

Russell, Jennifer ^{[1
]}

Eguchi, Masakatsu ^{[3
]}

Golubeva, Diana ^{[2
]}

Graham, Monica ^{[1
]}

Xenocostas, Anargyros ^{[4
]}

Trus, Michael R. ^{[5
]}

Foley, Ronan ^{[5
]}

Leber, Brian ^{[5
]}

Collins, Tony J. ^{[1
]}

Bhatia, Mickie ^{[1
,2
]}

机构：

[1] McMaster Univ, McMaster Stem Cell & Canc Res Inst, Fac Hlth Sci, 1280 Main St West,MDCL 5029, Hamilton, ON L8S 4L8, Canada

[2] McMaster Univ, Fac Hlth Sci, Dept Biochem & Biomed Sci, 1280 Main St West, Hamilton, ON L8S 4L8, Canada

[3] Theriac Pharmaceut Corp, Res Inst, 600 Broadway,Suite 580 Fl 5, Seattle, WA 98122 USA

[4] Univ Western Ontario, Schulich Sch Med, Dept Med, Div Hematol, London, ON N6A 3K7, Canada

[5] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4L8, Canada

来源：

CELL CHEMICAL BIOLOGY | 2017年 / 24卷 / 07期

关键词：

RNA-BINDING PROTEIN; SMALL-MOLECULE INHIBITOR; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER; WNT/BETA-CATENIN; HEMATOPOIETIC STEM; CBP; PHOSPHORYLATION; TRANSFORMATION; PROLIFERATION;

D O I：

10.1016/j.chembiol.2017.05.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：833 / +

页数：21

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