PMID- 14704789
OWN - NLM
STAT- MEDLINE
DCOM- 20040406
LR  - 20220317
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 10
IP  - 2
DP  - 2004 Feb
TI  - Expression profiling identifies the cytoskeletal organizer ezrin and the 
      developmental homeoprotein Six-1 as key metastatic regulators.
PG  - 175-81
AB  - Patients presenting with metastatic rhabdomyosarcoma (RMS), the most common 
      soft-tissue sarcoma in children, have a very poor clinical prognosis. This is 
      due, in large part, to our rudimentary knowledge of the molecular events that 
      dictate metastatic potential. We used cDNA microarray analysis of RMS cell lines, 
      derived from Ink4a/Arf-deficient mice transgenic for hepatocyte growth 
      factor/scatter factor (HGF/SF), to identify a set of genes whose expression was 
      significantly different between highly and poorly metastatic cells. Subsequent in 
      vivo functional studies revealed that the actin filament-plasma membrane linker 
      ezrin (encoded by Vil2) and the homeodomain-containing transcription factor Six-1 
      (sine oculis-related homeobox-1 homolog) had essential roles in determining the 
      metastatic fate of RMS cells. VIL2 and SIX1 expression was enhanced in human RMS 
      tissue, significantly correlating with clinical stage. The identification of 
      ezrin and Six-1 as critical regulators of metastasis in RMS provides new 
      mechanistic and therapeutic insights into this pediatric cancer.
FAU - Yu, Yanlin
AU  - Yu Y
AD  - Laboratory of Molecular Biology, National Cancer Institute, National Institutes 
      of Health, Bethesda, Maryland 20892, USA.
FAU - Khan, Javed
AU  - Khan J
FAU - Khanna, Chand
AU  - Khanna C
FAU - Helman, Lee
AU  - Helman L
FAU - Meltzer, Paul S
AU  - Meltzer PS
FAU - Merlino, Glenn
AU  - Merlino G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040104
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (SIX1 protein, human)
RN  - 0 (Six1 protein, mouse)
RN  - 0 (ezrin)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Child
MH  - Cytoskeletal Proteins
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - *Neoplasm Metastasis
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phenotype
MH  - Phosphoproteins/genetics/*metabolism
MH  - Phylogeny
MH  - Rhabdomyosarcoma/*metabolism/pathology/*secondary
EDAT- 2004/01/06 05:00
MHDA- 2004/04/07 05:00
CRDT- 2004/01/06 05:00
PHST- 2003/09/09 00:00 [received]
PHST- 2003/11/04 00:00 [accepted]
PHST- 2004/01/06 05:00 [pubmed]
PHST- 2004/04/07 05:00 [medline]
PHST- 2004/01/06 05:00 [entrez]
AID - nm966 [pii]
AID - 10.1038/nm966 [doi]
PST - ppublish
SO  - Nat Med. 2004 Feb;10(2):175-81. doi: 10.1038/nm966. Epub 2004 Jan 4.