PMID- 21076395
OWN - NLM
STAT- MEDLINE
DCOM- 20110124
LR  - 20211020
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 16
IP  - 12
DP  - 2010 Dec
TI  - Loss of the tumor suppressor Snf5 leads to aberrant activation of the 
      Hedgehog-Gli pathway.
PG  - 1429-33
LID - 10.1038/nm.2251 [doi]
AB  - Aberrant activation of the Hedgehog (Hh) pathway can drive tumorigenesis. To 
      investigate the mechanism by which glioma-associated oncogene family zinc 
      finger-1 (GLI1), a crucial effector of Hh signaling, regulates Hh pathway 
      activation, we searched for GLI1-interacting proteins. We report that the 
      chromatin remodeling protein SNF5 (encoded by SMARCB1, hereafter called SNF5), 
      which is inactivated in human malignant rhabdoid tumors (MRTs), interacts with 
      GLI1. We show that Snf5 localizes to Gli1-regulated promoters and that loss of 
      Snf5 leads to activation of the Hh-Gli pathway. Conversely, re-expression of SNF5 
      in MRT cells represses GLI1. Consistent with this, we show the presence of a 
      Hh-Gli-activated gene expression profile in primary MRTs and show that GLI1 
      drives the growth of SNF5-deficient MRT cells in vitro and in vivo. Therefore, 
      our studies reveal that SNF5 is a key mediator of Hh signaling and that aberrant 
      activation of GLI1 is a previously undescribed targetable mechanism contributing 
      to the growth of MRT cells.
FAU - Jagani, Zainab
AU  - Jagani Z
AD  - Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
FAU - Mora-Blanco, E Lorena
AU  - Mora-Blanco EL
FAU - Sansam, Courtney G
AU  - Sansam CG
FAU - McKenna, Elizabeth S
AU  - McKenna ES
FAU - Wilson, Boris
AU  - Wilson B
FAU - Chen, Dongshu
AU  - Chen D
FAU - Klekota, Justin
AU  - Klekota J
FAU - Tamayo, Pablo
AU  - Tamayo P
FAU - Nguyen, Phuong T L
AU  - Nguyen PT
FAU - Tolstorukov, Michael
AU  - Tolstorukov M
FAU - Park, Peter J
AU  - Park PJ
FAU - Cho, Yoon-Jae
AU  - Cho YJ
FAU - Hsiao, Kathy
AU  - Hsiao K
FAU - Buonamici, Silvia
AU  - Buonamici S
FAU - Pomeroy, Scott L
AU  - Pomeroy SL
FAU - Mesirov, Jill P
AU  - Mesirov JP
FAU - Ruffner, Heinz
AU  - Ruffner H
FAU - Bouwmeester, Tewis
AU  - Bouwmeester T
FAU - Luchansky, Sarah J
AU  - Luchansky SJ
FAU - Murtie, Joshua
AU  - Murtie J
FAU - Kelleher, Joseph F
AU  - Kelleher JF
FAU - Warmuth, Markus
AU  - Warmuth M
FAU - Sellers, William R
AU  - Sellers WR
FAU - Roberts, Charles W M
AU  - Roberts CW
FAU - Dorsch, Marion
AU  - Dorsch M
LA  - eng
GR  - R01 CA109467/CA/NCI NIH HHS/United States
GR  - R01 CA113794/CA/NCI NIH HHS/United States
GR  - R01 CA121941/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20101114
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GLI1 protein, human)
RN  - 0 (SMARCB1 Protein)
RN  - 0 (SMARCB1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
SB  - IM
CIN - Nat Med. 2010 Dec;16(12):1374-6. PMID: 21135845
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chromatin Immunoprecipitation
MH  - Chromosomal Proteins, Non-Histone/genetics/*metabolism
MH  - DNA Primers/genetics
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Humans
MH  - Immunoblotting
MH  - In Situ Hybridization
MH  - Mass Spectrometry
MH  - Mice
MH  - Microarray Analysis
MH  - Rhabdoid Tumor/*genetics
MH  - SMARCB1 Protein
MH  - Signal Transduction/*genetics
MH  - Transcription Factors/genetics/*metabolism
MH  - Zinc Finger Protein GLI1
PMC - PMC3859448
MID - NIHMS534776
COIS- COMPETING FINANCIAL INTERESTS The authors declare competing financial interests: 
      details accompany the full-text HTML version of the paper at 
      http://www.nature.com/naturemedicine/.
EDAT- 2010/11/16 06:00
MHDA- 2011/01/25 06:00
PMCR- 2013/12/11
CRDT- 2010/11/16 06:00
PHST- 2010/03/25 00:00 [received]
PHST- 2010/09/30 00:00 [accepted]
PHST- 2010/11/16 06:00 [entrez]
PHST- 2010/11/16 06:00 [pubmed]
PHST- 2011/01/25 06:00 [medline]
PHST- 2013/12/11 00:00 [pmc-release]
AID - nm.2251 [pii]
AID - 10.1038/nm.2251 [doi]
PST - ppublish
SO  - Nat Med. 2010 Dec;16(12):1429-33. doi: 10.1038/nm.2251. Epub 2010 Nov 14.