9月7日,，Cell Research雜志在線發(fā)表了上海生科院生化與細(xì)胞所宋建國研究組取得的研究成果：FOXA2 抑制人肺癌細(xì)胞的轉(zhuǎn)移是通過抑制EMT 來實(shí)現(xiàn)的,。
腫瘤是人類健康的最大威脅之一，90%的腫瘤患者都是死于腫瘤轉(zhuǎn)移,。越來越多的研究表明，EMT (epithelial-mesenchymal transition) 是調(diào)控腫瘤轉(zhuǎn)移的重要機(jī)制之一,。FOXA2在生物個體發(fā)育和代謝動態(tài)平衡中起著重要的作用,，但是FOXA2 是否在腫瘤轉(zhuǎn)移和TGF-β1誘導(dǎo)的EMT 中起作用依然不清楚,。
宋建國研究組的唐運(yùn)能博士等人通過實(shí)驗(yàn)研究發(fā)現(xiàn),，F(xiàn)OXA2 的表達(dá)水平與人肺癌細(xì)胞的遷移能力成負(fù)相關(guān)性，TGF-β1可以顯著的下調(diào)FOXA2蛋白水平,；在人肺癌細(xì)胞中下調(diào)FOXA2可以誘導(dǎo)人肺癌細(xì)胞發(fā)生EMT,，而過表達(dá)FOXA2 則可以抑制TGF-β1誘導(dǎo)的EMT。研究還表明,，F(xiàn)OXA2是通過抑制 slug 的轉(zhuǎn)錄來調(diào)控EMT的,；FOXA2還可以通過一段保守的DNA結(jié)合結(jié)構(gòu)域直接結(jié)合到slug 的啟動子上，進(jìn)而通過自身的轉(zhuǎn)活化區(qū)域 II （ transactivation region II）抑制slug 的轉(zhuǎn)錄,，從而抑制EMT和腫瘤細(xì)胞的轉(zhuǎn)移 ,。
該研究工作得到國家自然科學(xué)基金委、中國科學(xué)院,、科技部重大科學(xué)研究計劃,、上海市科委的經(jīng)費(fèi)資助。（生物谷Bioon.com）
生物谷近期特別推薦會議：
2010細(xì)胞治療研究進(jìn)展與臨床應(yīng)用前沿研討會 www.Cell-therapies.net 2010年9月23日-25日天津召開
第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)國際研討會 www.cancerasia.org 2010年10月12日-10月15日上海召開
生物谷推薦英文摘要：
Cell Res. doi:10.1038/cr.2010.126.
FOXA2 functions as a suppressor of tumor metastasis by inhibition of epithelial-to-mesenchymal transition in human lung cancers.
Tang Y, Shu G, Yuan X, Jing N, Song J.
The forkhead box transcription factor A2 (FOXA2) is an important regulator in animal development and body homeostasis. However, whether FOXA2 is involved in transforming growth factor beta1 (TGF-beta1)-mediated epithelial-to-mesenchymal transition (EMT) and tumor metastasis remains unknown. The present study showed that in human lung cancer cell lines, the abundance of FOXA2 positively correlates with epithelial phenotypes and negatively correlates with the mesenchymal phenotypes of cells, and TGF-beta1 treatment decreased FOXA2 protein level. Consistently, knockdown of FOXA2 promoted EMT and invasion of lung cancer cells, whereas overexpression of FOXA2 reduced the invasion and suppressed TGF-beta1-induced EMT. In addition, knockdown of FOXA2 induced slug expression, and ectopic expression of FOXA2 inhibited slug transcription. Furthermore, we identified that FOXA2 can bind to slug promoter through a conserved binding site, and that the DNA-binding region and transactivation region II of FOXA2 are required for repression of the slug promoter. These data demonstrate that FOXA2 functions as a suppressor of tumor metastasis by inhibition of EMT.
