A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells

Jlenia Guarnerio, Luisa Riccardi, Riccardo Taulli, Takahiro Maeda, Guocan Wang, Robin M. Hobbs, Min Sup Song, Paolo Sportoletti, Rosa Bernardi, Roderick T. Bronson, Mireia Castillo-Martin, Carlos Cordon-Cardo, Andrea Lunardi, Pier Paolo Pandolfi

研究成果: Contribution to journalArticle査読

12 被引用数 (Scopus)

抄録

The regulatory factors governing adult mesenchymal stem cell (MSC) physiology and their tumorigenic potential are still largely unknown, which substantially delays the identification of effective therapeutic approaches for the treatment of aggressive and lethal forms of MSC-derived mesenchymal tumors, such as undifferentiated sarcomas. Here, we have developed a novel platform to screen and quickly identify genes and pathways responsible for adult MSC transformation, modeled undifferentiated sarcoma in vivo , and, ultimately, tested the efficacy of targeting the identified oncopathways. Importantly, by taking advantage of this new platform, we demonstrate the key role of an aberrant LRF–DLK1–SOX9 pathway in the pathogenesis of undifferentiated sarcoma, with important therapeutic implications. SIGNIFICANCE: The paucity of therapeutic options for the treatment of sarcoma calls for a rapid and effective preclinical assessment of new therapeutic modalities. We have here developed a new platform to deconstruct the molecular genetics underlying the pathogenesis of sarcoma and to evaluate in vivo the efficacy of novel targeted therapies.

本文言語英語
ページ(範囲)396-409
ページ数14
ジャーナルCancer Discovery
5
4
DOI
出版ステータス出版済み - 4 1 2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学

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