Epigenetic antagonism between polycomb and SWI/SNF coomplexes during oncogenic transformation (Cancer Cell, 2010, 18:316-328)

報告日期: 2011/03/18
報告時間: 15:10/16:00
報告學生: 湯硯安 (英文報告)
講評老師: 王育民

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0318-1.pdf

Epigenetic Antagonism between Polycomb and SWI/SNF Complexes during Oncogenic Transformation

Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME, Cho YJ, Koellhoffer EC, Pomeroy SL, Orkin SH, Roberts CW
Cancer Cell 18, 316–328, October 19, 2010

Speaker: Yen-An Tang (湯硯安)
Commentator: Dr. Ju-Ming Wang (王育民教授)
Date: 2011/03/18 (pm 17:10-18:00)
Room: 602

Background: It is difficult to dissect the roles of epigenetic alterations in tumorigenesis because of the prevalent occurrence of genomic instability and genetic mutation in cancers. SNF5 is a core subunit of SWI/SNF chromatin remodeling complex, and has been identified to be initiation of malignant rhabdoid tumor due to the germ line and somatic mutation of SNF5. SNF5-deficient cancers, despite being highly aggressive, are diploid and genomically stable, make it an idea model to explore the purpose. In addition, Polycomb group (PcG) has been identified to be responsible for stem cell pluripotency as well as oncogenic transformation. It is reported that antagonism relationship between PcG and SWI/SNF complexes in Drosophila, however, this relationship has not been checked in human cancers.
Objective: To investigate the relationship between SNF5 and PcG protein, EZH2, in oncogenic transformation.
Results: The author found that EZH2 protein level is upregulated in SNF5-deficient cancers or in SNF-5 inactivating mouse embryonic fibroblasts, which was possibly resulted from loss of SNF5-mediated repression on EZH2 gene. In addition, SNF5 and EZH2 had antagonist roles in the control of target gene expression. Thus, loss of SNF5 resulted in increased level of EZH2 and histone H3K27 tri-methylation at target genes, leading to silence of these genes. Moreover, SNF5 loss activated stem cell-associated programs. Finally, inactivation of EZH2 could suppress tumor formation driven by SNF5-deficiency. Collectively, this study provides evidence that epigenetic alterations play important roles in tumor formation, and suggests EZH2 is putative target for cancer therapeutics.

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