Dystrophin Is a Tumor Suppressor in Human Cancers with Myogenic Programs
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Author
Marino-Enriquez, Adrian
Bennett, Richard R.
Shen, Yiping
Eilers, Grant
Lee, Jen-Chieh
Henze, Joern
Fletcher, Benjamin S.
Gu, Zhizhan
Fox, Edward A.
Antonescu, Cristina R.
Guo, Xiangqian
van de Rijn, Matt
Ordog, Tamas
Kunkel, Louis M.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.2974Metadata
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Wang, Y., A. Marino-Enriquez, R. R. Bennett, M. Zhu, Y. Shen, G. Eilers, J. Lee, et al. 2014. “Dystrophin Is a Tumor Suppressor in Human Cancers with Myogenic Programs.” Nature genetics 46 (6): 601-606. doi:10.1038/ng.2974. http://dx.doi.org/10.1038/ng.2974.Abstract
Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS), and leiomyosarcoma (LMS), feature myogenic differentiation1–3. Here we report that intragenic deletion of the dystrophin-encoding and muscular dystrophy-associated DMD gene is a frequent mechanism by which myogenic tumors progress to high-grade, lethal sarcomas. Dystrophin is expressed in nonneoplastic and benign counterparts for GIST, RMS and LMS, and the DMD deletions inactivate larger dystrophin isoforms, including 427kDa dystrophin, while preserving expression of an essential 71kDa isoform. Dystrophin inhibits myogenic sarcoma cell migration, invasion, anchorage independence, and invadopodia formation, and dystrophin inactivation was found in 96%, 100%, and 62% of metastatic GIST, embryonal RMS, and LMS, respectively. These findings validate dystrophin as a tumor suppressor and likely anti-metastatic factor, suggesting that therapies in development for muscular dystrophies may also have relevance in treatment of cancer.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225780/pdf/Terms of Use
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