Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma

• DOI: 10.1073/pnas.1317731111
• Publication Date: 2014-03-25T05:25:24Z
• Authors: Eleanor Y. Chen; Michael T. DeRan; Myron S. Ignatius; Kathryn Brooke Gr...; Ryan Clagg; Karin M. McCarthy; Riadh M. Lobbardi; Jillian Brockmann; Charles Keller; Xu Wu; David M. Langenau
• Keywords: 0301 basic medicine; Glycogen Synthase Kinase 3; 03 medical and health sciences; Animals; Humans; Rhabdomyosarcoma, Embryonal; Enzyme Inhibitors; Wnt Signaling Pathway; Zebrafish; beta Catenin; Cell Line; 3. Good health

Significance Embryonal rhabdomyosarcoma (ERMS) is a cancer of skeletal muscle and is one of the most common pediatric cancers of soft tissue. There is no effective treatment for patients with relapsed ERMS, with less than 50% surviving the disease. The self-renewing and molecularly defined tumor propagating cells (TPCs) drive continued tumor growth and relapse. Yet to date, drugs targeting ERMS self-renewal and differentiation of TPCs have not been identified. Our study describes a large-scale chemical screen to identify targetable pathways essential for modulating self-renewal and differentiation of ERMS and demonstrates the feasibility of inducing differentiation of TPCs in ERMS by small molecules.