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Cancer Cell:能抑制大肠癌向肝脏和肺转移的基因

来源:新华社 2011-01-24 13:42

日本研究人员新发现一种能够抑制大肠癌向肝脏和肺转移的基因,这项成果可能有助于开发抑制大肠癌转移的药物,相关论文发表在19日的美国科学杂志《癌细胞》网络版上。

在日本的癌症患者中,因大肠癌死亡的人数一直居高不下,在男性患者中居第三位,在女性患者中居第一位。如果大肠癌未向其他脏器转移,患者的5年生存率可达80%至90%,而一旦出现转移,则降低到10%至20%。

京都大学、东北大学和金泽大学的联合研究小组发现,在大肠癌转移到肝脏的患者体内,一种被称为Aes的基因功能较弱。动物实验显示,如果强制患有大肠癌的小鼠体内的Aes基因发挥作用,则癌细胞转移到肝脏和肺的比例比对照组低20%至30%,这证明Aes基因具有抑制大肠癌转移的作用。

研究人员进而确认,一种称为“Notch信号传导”的反应能促进大肠癌细胞侵入血管内部开始转移,而Aes基因合成的蛋白质会阻碍这种信号传导。如果Aes基因的功能减弱,制造出的蛋白质减少,癌细胞就会进一步扩散。不过目前尚不清楚Aes基因功能减弱的机制。

京都大学教授武藤诚指出,这一成果有助于开发出抑制大肠癌扩散和转移的药物。(生物谷Bioon.com)

生物谷推荐原文出处:

Cancer Cell  doi:10.1016/j.ccr.2010.11.008

Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling

Masahiro 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 Mark Taketo

Highlights

Aes suppresses colon cancer metastasis in an orthotopic transplantation model

Aes is an endogenous inhibitor of Notch signaling

Notch signaling is activated in cancer cells by ligands on stromal cells

Aes knockout in ApcΔ716 mice cause local invasion and intravasation of tumor cells

Summary

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 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.

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