PMID- 21251616
OWN - NLM
STAT- MEDLINE
DCOM- 20110314
LR  - 20220311
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Linking)
VI  - 19
IP  - 1
DP  - 2011 Jan 18
TI  - Suppression of colon cancer metastasis by Aes through inhibition of Notch 
      signaling.
PG  - 125-37
LID - 10.1016/j.ccr.2010.11.008 [doi]
AB  - Metastasis is responsible for most cancer deaths. Here, we show that Aes (or 
      Grg5) gene functions as an endogenous metastasis suppressor. Expression of Aes 
      was decreased in liver metastases compared with primary colon tumors in both mice 
      and humans. Aes inhibited Notch signaling by converting active Rbpj transcription 
      complexes into repression complexes on insoluble nuclear matrix. In tumor cells, 
      Notch signaling was triggered by ligands on adjoining blood vessels, and 
      stimulated transendothelial migration. Genetic depletion of Aes in Apc(Delta716) 
      intestinal polyposis mice caused marked tumor invasion and intravasation that 
      were suppressed by Notch signaling inhibition. These results suggest that 
      inhibition of Notch signaling can be a promising strategy for prevention and 
      treatment of colon cancer metastasis.
CI  - Copyright A(c) 2011 Elsevier Inc. All rights reserved.
FAU - Sonoshita, Masahiro
AU  - Sonoshita M
AD  - Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 
      606-8501, Japan.
FAU - Aoki, Masahiro
AU  - Aoki M
FAU - Fuwa, Haruhiko
AU  - Fuwa H
FAU - Aoki, Koji
AU  - Aoki K
FAU - Hosogi, Hisahiro
AU  - Hosogi H
FAU - Sakai, Yoshiharu
AU  - Sakai Y
FAU - Hashida, Hiroki
AU  - Hashida H
FAU - Takabayashi, Arimichi
AU  - Takabayashi A
FAU - Sasaki, Makoto
AU  - Sasaki M
FAU - Robine, Sylvie
AU  - Robine S
FAU - Itoh, Kazuyuki
AU  - Itoh K
FAU - Yoshioka, Kiyoko
AU  - Yoshioka K
FAU - Kakizaki, Fumihiko
AU  - Kakizaki F
FAU - Kitamura, Takanori
AU  - Kitamura T
FAU - Oshima, Masanobu
AU  - Oshima M
FAU - Taketo, Makoto Mark
AU  - Taketo MM
LA  - eng
SI  - GEO/GSE12162
GR  - G1002033/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 
      (2-(((3,5-difluorophenyl)acetyl)amino)-N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl)propanamide)
RN  - 0 (Benzodiazepinones)
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
RN  - 0 (Ligands)
RN  - 0 (Notch1 protein, mouse)
RN  - 0 (Rbpj protein, mouse)
RN  - 0 (Receptor, Notch1)
RN  - 0 (Receptors, Notch)
RN  - 0 (Repressor Proteins)
RN  - 0 (TLE5 protein, human)
RN  - 0 (Tle1 protein, mouse)
RN  - 0 (Tle5 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
CIN - Cancer Cell. 2011 Jan 18;19(1):6-8. PMID: 21251610
MH  - Animals
MH  - Benzodiazepinones/pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Co-Repressor Proteins
MH  - Colonic Neoplasms/drug therapy/metabolism/*pathology
MH  - Down-Regulation/genetics
MH  - Gene Expression/genetics
MH  - Gene Silencing/physiology
MH  - HCT116 Cells
MH  - Humans
MH  - Immunoglobulin J Recombination Signal Sequence-Binding 
      Protein/genetics/metabolism
MH  - Intestinal Polyposis/drug therapy/metabolism/pathology
MH  - Ligands
MH  - Liver Neoplasms/pathology/secondary
MH  - Lung Neoplasms/pathology/prevention & control/secondary
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Mice, Nude
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Neoplasm Invasiveness/genetics/pathology/prevention & control
MH  - Neoplasm Metastasis/genetics/pathology/prevention & control
MH  - Nuclear Matrix/metabolism
MH  - Receptor, Notch1/metabolism
MH  - Receptors, Notch/antagonists & inhibitors/*metabolism
MH  - Repressor Proteins/genetics/metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - Stromal Cells/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Transendothelial and Transepithelial Migration/physiology
EDAT- 2011/01/22 06:00
MHDA- 2011/03/15 06:00
CRDT- 2011/01/22 06:00
PHST- 2010/06/07 00:00 [received]
PHST- 2010/09/17 00:00 [revised]
PHST- 2010/11/02 00:00 [accepted]
PHST- 2011/01/22 06:00 [entrez]
PHST- 2011/01/22 06:00 [pubmed]
PHST- 2011/03/15 06:00 [medline]
AID - S1535-6108(10)00473-3 [pii]
AID - 10.1016/j.ccr.2010.11.008 [doi]
PST - ppublish
SO  - Cancer Cell. 2011 Jan 18;19(1):125-37. doi: 10.1016/j.ccr.2010.11.008.