Author/Authors :
Sonoshita، نويسنده , , Masahiro and Aoki، نويسنده , , Masahiro and Fuwa، نويسنده , , Haruhiko and Aoki، نويسنده , , Koji and Hosogi، نويسنده , , Hisahiro and Sakai، نويسنده , , Yoshiharu and Hashida، نويسنده , , Hiroki and Takabayashi، نويسنده , , Arimichi and Sasaki، نويسنده , , Makoto and Robine، نويسنده , , Sylvie and Itoh، نويسنده , , Kazuyuki and Yoshioka، نويسنده , , Kiyoko and Kakizaki، نويسنده , , Fumihiko and Kitamura، نويسنده , , Takanori and Oshima، نويسنده , , Masanobu and Taketo، نويسنده , , Makoto Mark، نويسنده ,
Abstract :
Summary
asis 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 ApcΔ716 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.
