9月7日，Cell Research杂志在线发表了上海生科院生化与细胞所宋建国研究组取得的研究成果：FOXA2 抑制人肺癌细胞的转移是通过抑制EMT 来实现的。
肿瘤是人类健康的最大威胁之一，90%的肿瘤患者都是死于肿瘤转移。越来越多的研究表明，EMT (epithelial-mesenchymal transition) 是调控肿瘤转移的重要机制之一。FOXA2在生物个体发育和代谢动态平衡中起着重要的作用，但是FOXA2 是否在肿瘤转移和TGF-β1诱导的EMT 中起作用依然不清楚。
宋建国研究组的唐运能博士等人通过实验研究发现，FOXA2 的表达水平与人肺癌细胞的迁移能力成负相关性，TGF-β1可以显着的下调FOXA2蛋白水平；在人肺癌细胞中下调FOXA2可以诱导人肺癌细胞发生EMT，而过表达FOXA2 则可以抑制TGF-β1诱导的EMT。研究还表明，FOXA2是通过抑制 slug 的转录来调控EMT的；FOXA2还可以通过一段保守的DNA结合结构域直接结合到slug 的启动子上，进而通过自身的转活化区域 II （ transactivation region II）抑制slug 的转录，从而抑制EMT和肿瘤细胞的转移 。
该研究工作得到国家自然科学基金委、中国科学院、科技部重大科学研究计划、上海市科委的经费资助。（生物谷Bioon.com）
生物谷近期特别推荐会议：
2010细胞治疗研究进展与临床应用前沿研讨会 www.Cell-therapies.net 2010年9月23日-25日天津召开
第一届肿瘤基础和转化医学国际研讨会 www.cancerasia.org 2010年10月12日-10月15日上海召开
生物谷推荐英文摘要：
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.
