Facilitates Chromatin Transcription Complex Is an "Accelerator'' of Tumor Transformation and Potential Marker and Target of Aggressive Cancers

被引:103
作者
Garcia, Henry [1 ]
Miecznikowski, Jeffrey C. [2 ]
Safina, Alfiya [1 ]
Commane, Mairead [1 ]
Ruusulehto, Anja [3 ]
Kilpinen, Sami [3 ]
Leach, Robert W. [4 ]
Attwood, Kristopher [5 ]
Li, Yan [5 ]
Degan, Seamus [1 ]
Omilian, Angela R. [6 ]
Guryanova, Olga [7 ]
Papantonopoulou, Olympia [1 ]
Wang, Jianmin [5 ]
Buck, Michael [8 ]
Liu, Song [5 ]
Morrison, Carl [6 ]
Gurova, Katerina V. [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA
[2] SUNY Buffalo, Dept Biostat, Buffalo, NY 14263 USA
[3] MediSapiens Ltd, Helsinki 00290, Finland
[4] SUNY Buffalo, Ctr Computat Res, Buffalo, NY 14263 USA
[5] Roswell Pk Canc Inst, Dept Biostat & Bioinformat, Buffalo, NY 14263 USA
[6] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA
[7] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA
[8] SUNY Buffalo, Dept Biochem, Buffalo, NY 14263 USA
来源
CELL REPORTS | 2013年 / 4卷 / 01期
关键词
MAMMARY EPITHELIAL-CELLS; FUNCTIONAL COOPERATION; INTERACTION NETWORK; DNA-REPLICATION; FACT; SSRP1; EXPRESSION; PROTEIN; P53; ARABIDOPSIS;
D O I
10.1016/j.celrep.2013.06.013
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The facilitates chromatin transcription (FACT) complex is involved in chromatin remodeling during transcription, replication, and DNA repair. FACT was previously considered to be ubiquitously expressed and not associated with any disease. However, we discovered that FACT is the target of a class of anticancer compounds and is not expressed in normal cells of adult mammalian tissues, except for undifferentiated and stem-like cells. Here, we show that FACT expression is strongly associated with poorly differentiated aggressive cancers with low overall survival. In addition, FACT was found to be upregulated during in vitro transformation and to be necessary, but not sufficient, for driving transformation. FACT also promoted survival and growth of established tumor cells. Genome-wide mapping of chromatin-bound FACT indicated that FACT's role in cancer most likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses.
引用
收藏
页码:159 / 173
页数:15
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