Enhancer of zeste homolog 2 (EZH2) in pediatric soft tissue sarcomas: first implications

BMC Medicine

Minireview

Lucio Miele¹  Rossella Rota²  Roberta Ciarapica²  Franco Locatelli³  Antonio Giordano⁴ 

[1]Cancer Institute, University of Mississippi Medical Center, Jackson, MI, USA

[2]Department of Oncohematology, IRCCS, Ospedale Pediatrico Bambino Gesù, Roma, Italy

[3]Department of Oncohematology, IRCCS, Ospedale Pediatrico Bambino Gesù, Roma, Italy

[4]Dipartimento di Scienze Pediatriche, Università di Pavia, Pavia, Italy

[5]Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA

[6]Department of Human Pathology and Oncology, Università of Siena, Siena, Italy

关键词: EZH2;    soft tissue sarcomas;    epigenetics;    methylation;    methyltransferases;   

DOI  :  10.1186/1741-7015-9-63

 received in 2011-02-02, accepted in 2011-05-25,  发布年份 2011

来源: Springer

【 摘 要 】

Soft tissue sarcomas of childhood are a group of heterogeneous tumors thought to be derived from mesenchymal stem cells. Surgical resection is effective only in about 50% of cases and resistance to conventional chemotherapy is often responsible for treatment failure. Therefore, investigations on novel therapeutic targets are of fundamental importance. Deregulation of epigenetic mechanisms underlying chromatin modifications during stem cell differentiation has been suggested to contribute to soft tissue sarcoma pathogenesis. One of the main elements in this scenario is enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to the Polycomb group proteins. EZH2 catalyzes histone H3 methylation on gene promoters, thus repressing genes that induce stem cell differentiation to maintain an embryonic stem cell signature. EZH2 deregulated expression/function in soft tissue sarcomas has been recently reported. In this review, an overview of the recently reported functions of EZH2 in soft tissue sarcomas is given and the hypothesis that its expression might be involved in soft tissue sarcomagenesis is discussed. Finally, the therapeutic potential of epigenetic therapies modulating EZH2-mediated gene repression is considered.

【 授权许可】

CC BY   
© Ciarapica et al; licensee BioMed Central Ltd. 2011