Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling
2011; Cell Press; Volume: 19; Issue: 1 Linguagem: Inglês
10.1016/j.ccr.2010.11.008
ISSN1878-3686
AutoresMasahiro Sonoshita, Masahiro Aoki, Haruhiko Fuwa, Koji Aoki, Hisahiro Hosogi, Yoshiharu Sakai, Hiroki Hashida, Arimichi Takabayashi, Makoto Sasaki, Sylvie Robine, Kazuyuki Itoh, Kiyoko Yoshioka, Fumihiko Kakizaki, Takanori Kitamura, Masanobu Oshima, Makoto M. Taketo,
Tópico(s)Epigenetics and DNA Methylation
ResumoSummary 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.
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