日本研究人員新發(fā)現(xiàn)一種能夠抑制大腸癌向肝臟和肺轉(zhuǎn)移的基因，這項成果可能有助于開發(fā)抑制大腸癌轉(zhuǎn)移的藥物,，相關(guān)論文發(fā)表在19日的美國科學雜志《癌細胞》網(wǎng)絡(luò)版上,。
在日本的癌癥患者中,，因大腸癌死亡的人數(shù)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,。如果大腸癌未向其他臟器轉(zhuǎn)移，患者的5年生存率可達80%至90%,，而一旦出現(xiàn)轉(zhuǎn)移,，則降低到10%至20%。
京都大學,、東北大學和金澤大學的聯(lián)合研究小組發(fā)現(xiàn),，在大腸癌轉(zhuǎn)移到肝臟的患者體內(nèi)，一種被稱為Aes的基因功能較弱,。動物實驗顯示,，如果強制患有大腸癌的小鼠體內(nèi)的Aes基因發(fā)揮作用，則癌細胞轉(zhuǎn)移到肝臟和肺的比例比對照組低20%至30%,，這證明Aes基因具有抑制大腸癌轉(zhuǎn)移的作用,。
研究人員進而確認，一種稱為“Notch信號傳導(dǎo)”的反應(yīng)能促進大腸癌細胞侵入血管內(nèi)部開始轉(zhuǎn)移,，而Aes基因合成的蛋白質(zhì)會阻礙這種信號傳導(dǎo),。如果Aes基因的功能減弱，制造出的蛋白質(zhì)減少,，癌細胞就會進一步擴散,。不過目前尚不清楚Aes基因功能減弱的機制。
京都大學教授武藤誠指出,，這一成果有助于開發(fā)出抑制大腸癌擴散和轉(zhuǎn)移的藥物,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
