https://scholars.lib.ntu.edu.tw/handle/123456789/473706
標題: | Dystrophin is a tumor suppressor in human cancers with myogenic programs | 作者: | Wang Y. Marino-Enriquez A. Bennett R.R. Zhu M. Shen Y. Eilers G. JEN-CHIEH LEE Henze J. Fletcher B.S. Gu Z. Fox E.A. Antonescu C.R. Fletcher C.D.M. Guo X. Raut C.P. Demetri G.D. Van De Rijn M. Ordog T. Kunkel L.M. Fletcher J.A. |
公開日期: | 2014 | 出版社: | Nature Publishing Group | 卷: | 46 | 期: | 6 | 起(迄)頁: | 601-606 | 來源出版物: | Nature Genetics | 摘要: | Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS), feature myogenic differentiation. 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 the non-neoplastic and benign counterparts of GIST, RMS and LMS tumors, and DMD deletions inactivate larger dystrophin isoforms, including 427-kDa dystrophin, while preserving the expression of an essential 71-kDa 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 samples, 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 the treatment of cancer. ? 2014 Nature America, Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84901680208&doi=10.1038%2fng.2974&partnerID=40&md5=5f1a2de05b1cbdbecb48ecbf4c2944af https://scholars.lib.ntu.edu.tw/handle/123456789/473706 |
ISSN: | 1061-4036 | DOI: | 10.1038/ng.2974 | SDG/關鍵字: | dystrophin; anchorage independent growth; article; cell invasion; cell migration; clinical article; controlled study; embryonal rhabdomyosarcoma; female; fluorescence in situ hybridization; gastrointestinal stromal tumor; gene deletion; gene expression; gene inactivation; human; human cell; human tissue; leiomyosarcoma; male; multiplex ligation dependent probe amplification; muscular dystrophy; nucleotide sequence; priority journal; sarcoma cell; single nucleotide polymorphism; transcription initiation site; tumor suppressor gene; X chromosome; Animals; Cell Differentiation; Cell Line, Tumor; Cell Movement; Disease Progression; Dystrophin; Female; Gastrointestinal Stromal Tumors; Gene Deletion; Genes, Tumor Suppressor; Humans; In Situ Hybridization, Fluorescence; Interstitial Cells of Cajal; Leiomyosarcoma; Male; Mice; Mice, Inbred BALB C; Muscle Development; Muscle, Skeletal; Muscular Dystrophies; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Rhabdomyosarcoma; Sarcoma |
顯示於: | 病理學科所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。