编码转录因子Krüppel样锌指蛋白ZNF217的基因是乳腺癌的候选癌基因。它促进乳腺癌发展的机理如何呢？5月23日Cancer Research 杂志在线发表了Pascale A Cohen研究组的研究论文阐明了其中的奥秘。
研究发现，在乳腺癌细胞中过表达ZNF217可在体外实验中提高癌细胞的迁移和侵袭能力，并在小鼠体内促进癌细胞向肺及淋巴结的自发转移。通过激活TGF-β激动的Smad信号通路，ZNF217也在人类乳腺上皮细胞中促进上皮-间叶组织转变（EMT）。此外，在ZNF217过表达乳腺上皮细胞中，由于ZNF217直接上调了TGFB2或者TGFB3的表达水平，从而导致一条TGF-β自分泌环路持续激活TGF-β信号途径，促进恶性表型。通过抑制TGF-β信号途径可以逆转ZNF217介导的EMT。
他们的研究还发现，ZNF217的mRNA水平可能作为乳腺癌预后的一项新的生物标志物。对于ZNF217表达水平高的乳腺癌患者，针对ZNF217-TGF-β信号途径的靶向性治疗可能是一个新的福音。（生物谷Bioon.com）
doi: 10.1158/0008-5472.CAN-11-3095
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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.
