PMID- 24069508
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130926
LR  - 20211021
IS  - 1947-6019 (Print)
IS  - 1947-6027 (Electronic)
IS  - 1947-6019 (Linking)
VI  - 4
IP  - 5-6
DP  - 2013 May
TI  - EWS and RE1-Silencing Transcription Factor Inhibit Neuronal Phenotype Development 
      and Oncogenic Transformation in Ewing Sarcoma.
PG  - 213-23
LID - 10.1177/1947601913489569 [doi]
AB  - The gene encoding EWS (EWSR1) is involved in various chromosomal translocations 
      that cause the production of oncoproteins responsible for multiple cancers 
      including Ewing sarcoma, myxoid liposarcoma, soft tissue clear cell sarcoma, and 
      desmoplastic small round cell sarcoma. It is well known that EWS fuses to FLI to 
      create EWS/FLI, which is the abnormal transcription factor that drives tumor 
      development in Ewing sarcoma. However, the role of wild-type EWS in Ewing sarcoma 
      pathogenesis remains unclear. In the current study, we identified EWS-regulated 
      genes and cellular processes through RNA interference combined with RNA 
      sequencing and functional annotation analyses. Interestingly, we found that EWS 
      and EWS/FLI co-regulate a significant cluster of genes, indicating an interplay 
      between the 2 proteins in regulating cellular functions. We found that among the 
      EWS-down-regulated genes are a subset of neuronal genes that contain binding 
      sites for the RE1-silencing transcription factor (REST or neuron-restrictive 
      silencer factor [NRSF]), neuron-restrictive silencer element (NRSE), suggesting a 
      cooperative interaction between REST and EWS in gene regulation. 
      Co-immunoprecipitation analysis demonstrated that EWS interacts directly with 
      REST. Genome-wide binding analysis showed that EWS binds chromatin at or near 
      NRSE. Furthermore, functional studies revealed that both EWS and REST inhibit 
      neuronal phenotype development and oncogenic transformation in Ewing sarcoma 
      cells. Our data implicate an important role of EWS in the development of Ewing 
      sarcoma phenotype and highlight a potential value in modulating EWS function in 
      the treatment of Ewing sarcoma and other EWS translocation-based cancers.
FAU - Sankar, Savita
AU  - Sankar S
AD  - Department of Oncological Sciences, University of Utah School of Medicine, Salt 
      Lake City, UT, USA.
FAU - Gomez, Nicholas C
AU  - Gomez NC
FAU - Bell, Russell
AU  - Bell R
FAU - Patel, Mukund
AU  - Patel M
FAU - Davis, Ian J
AU  - Davis IJ
FAU - Lessnick, Stephen L
AU  - Lessnick SL
FAU - Luo, Wen
AU  - Luo W
LA  - eng
GR  - K08 CA100400/CA/NCI NIH HHS/United States
GR  - P30 CA042014/CA/NCI NIH HHS/United States
GR  - R01 CA140394/CA/NCI NIH HHS/United States
GR  - R01 CA166447/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Genes Cancer
JT  - Genes & cancer
JID - 101516546
PMC - PMC3782006
OTO - NOTNLM
OT  - EWS
OT  - Ewing sarcoma
OT  - REST
OT  - neuronal phenotype
OT  - oncogenic transformation
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2013/09/27 06:00
MHDA- 2013/09/27 06:01
PMCR- 2013/05/01
CRDT- 2013/09/27 06:00
PHST- 2013/02/14 00:00 [received]
PHST- 2013/04/10 00:00 [accepted]
PHST- 2013/09/27 06:00 [entrez]
PHST- 2013/09/27 06:00 [pubmed]
PHST- 2013/09/27 06:01 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - 10.1177_1947601913489569 [pii]
AID - 10.1177/1947601913489569 [doi]
PST - ppublish
SO  - Genes Cancer. 2013 May;4(5-6):213-23. doi: 10.1177/1947601913489569.