編碼轉(zhuǎn)錄因子Krüppel樣鋅指蛋白ZNF217的基因是乳腺癌的候選癌基因。它促進(jìn)乳腺癌發(fā)展的機(jī)理如何呢,？5月23日Cancer Research 雜志在線發(fā)表了Pascale A Cohen研究組的研究論文闡明了其中的奧秘,。
研究發(fā)現(xiàn),，在乳腺癌細(xì)胞中過(guò)表達(dá)ZNF217可在體外實(shí)驗(yàn)中提高癌細(xì)胞的遷移和侵襲能力，并在小鼠體內(nèi)促進(jìn)癌細(xì)胞向肺及淋巴結(jié)的自發(fā)轉(zhuǎn)移,。通過(guò)激活TGF-β激動(dòng)的Smad信號(hào)通路,，ZNF217也在人類乳腺上皮細(xì)胞中促進(jìn)上皮-間葉組織轉(zhuǎn)變（EMT）。此外,，在ZNF217過(guò)表達(dá)乳腺上皮細(xì)胞中,，由于ZNF217直接上調(diào)了TGFB2或者TGFB3的表達(dá)水平，從而導(dǎo)致一條TGF-β自分泌環(huán)路持續(xù)激活TGF-β信號(hào)途徑,，促進(jìn)惡性表型,。通過(guò)抑制TGF-β信號(hào)途徑可以逆轉(zhuǎn)ZNF217介導(dǎo)的EMT。
他們的研究還發(fā)現(xiàn),，ZNF217的mRNA水平可能作為乳腺癌預(yù)后的一項(xiàng)新的生物標(biāo)志物,。對(duì)于ZNF217表達(dá)水平高的乳腺癌患者，針對(duì)ZNF217-TGF-β信號(hào)途徑的靶向性治療可能是一個(gè)新的福音,。（生物谷Bioon.com）
doi: 10.1158/0008-5472.CAN-11-3095
PMC:
PMID:
ZNF217 is a marker of poor prognosis in breast cancer that drives epithelial-mesenchymal transition and invasion
Julie A. Vendrell1, Aurélie Thollet1, Nhan T Nguyen1, Sandra E Ghayad1, Stéphanie Vinot2, Ivan Biéche3, Evelyne Grisard1, Véronique Josserand4, Jean-Luc Coll4, Pierre Roux2, Laura Corbo5, Isabelle Treilleux5, Ruth Rimokh5, and Pascale A Cohen6,*
The Krüppel-like zinc-finger protein ZNF217 is a candidate oncogene in breast cancer. In this study, we demonstrated that high levels of expression of ZNF217 mRNA are associated with poor prognosis and the development of metastases in breast cancer. Overexpression of ZNF217 in breast cancer cells stimulated migration and invasion in vitro and promoted the development of spontaneous lung or node metastases in mice in vivo. ZNF217 also promoted epithelial-mesenchymal transition (EMT) in human mammary epithelial cells, and the TGF-β-activated Smad signaling pathway was identified as a major driver of ZNF217-induced EMT. In addition, a TGF-β autocrine loop sustained activation of the TGF-β pathway in ZNF217-overexpressing mammary epithelial cells, most likely due to ZNF217-mediated direct up-regulation of TGFB2 or TGFB3. Inhibition of the TGF-β pathway led to the reversal of ZNF217-mediated EMT. Together, our findings indicate that ZNF217 mRNA expression may represent a novel prognostic biomarker in breast cancer. Therapeutic targeting of ZNF217 of the TGF-β signaling pathway may benefit the subset of patients whose tumors express high levels of ZNF217.
