@article{7f02baec3100491b86c27e6cae2c65e0,
title = "A Mouse Model of Rhabdomyosarcoma Originating from the Adipocyte Lineage",
abstract = "Rhabdomyosarcoma (RMS) is an aggressive skeletal muscle-lineage tumor composed of malignant myoblasts that fail to exit the cell cycle and are blocked from fusing into syncytial muscle. Rhabdomyosarcoma includes two histolopathologic subtypes: alveolar rhabdomyosarcoma, driven by the fusion protein PAX3-FOXO1 or PAX7-FOXO1, and embryonal rhabdomyosarcoma (ERMS), which is genetically heterogeneous. Here, we show that adipocyte-restricted activation of Sonic hedgehog signaling through expression of a constitutively active Smoothened allele in mice gives rise to aggressive skeletal muscle tumors that display the histologic and molecular characteristics of human ERMS with high penetrance. Our findings suggest that adipocyte progenitors can be a cell of origin for Sonic hedgehog-driven ERMS, showing that RMS can originate from nonskeletal muscle precursors.",
author = "Hatley, {Mark E.} and Wei Tang and Garcia, {Matthew R.} and David Finkelstein and Millay, {Douglas P.} and Ning Liu and Jonathan Graff and Galindo, {Rene L.} and Olson, {Eric N.}",
note = "Funding Information: We are grateful to Jose Cabrera for figure preparation and John Shelton for experimental assistance. We thank Nabeel Bardeesy for the Cdkn2a Flox mice. Work in E.N.O.{\textquoteright}s laboratory was supported by grants from the National Institutes of Health, the Leducq Foundation, the Robert A. Welch Foundation, and the Cancer Prevention and Research Institute of Texas. M.E.H. is supported by Alex{\textquoteright}s Lemonade Stand Foundation, Pediatric Scientist Development Program sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD Grant Award K12-HD000850), and the American Lebanese Syrian Associated Charities (ALSAC). Funding to R.L.G. for this work was provided by the Burroughs Wellcome Fund Career Award for Medical Scientists, the American Cancer Society/Simmons Cancer Center Institutional Research Grant (ACS-IRG-02-196), The CureSearch for Children{\textquoteright}s Cancer Young Investigator Program, and an Alex{\textquoteright}s Lemonade Stand Foundation “A” Award. Work in J. G.{\textquoteright}s lab was supported by NIDDK Grants R01-DK066566, R01-DK064261, and R01-DK088220. ",
year = "2012",
month = oct,
day = "16",
doi = "10.1016/j.ccr.2012.09.004",
language = "English (US)",
volume = "22",
pages = "536--546",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}