Format

Send to

Choose Destination
Cancer Cell. 2011 Jan 18;19(1):125-37. doi: 10.1016/j.ccr.2010.11.008.

Suppression of colon cancer metastasis by Aes through inhibition of Notch signaling.

Author information

1
Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

Abstract

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(Δ716) 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.

PMID:
21251616
DOI:
10.1016/j.ccr.2010.11.008
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances, Secondary source ID, Grant support

Publication type

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center