American Association for Cancer Research
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Supplementary Methods and Materials from ZNF217 Is a Marker of Poor Prognosis in Breast Cancer That Drives Epithelial–Mesenchymal Transition and Invasion

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journal contribution
posted on 2023-03-30, 21:01 authored by Julie A. Vendrell, Aurélie Thollet, Nhan T. Nguyen, Sandra E. Ghayad, Stéphanie Vinot, Ivan Bièche, Evelyne Grisard, Véronique Josserand, Jean-Luc Coll, Pierre Roux, Laura Corbo, Isabelle Treilleux, Ruth Rimokh, Pascale A. Cohen

PDF file - 107K, complementary information and methods on breast-tumor cohorts, HMLE cells and transcriptomic analysis



The Krüppel-like zinc finger protein ZNF217 is a candidate oncogene in breast cancer. In this study, we showed 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 because of ZNF217-mediated direct upregulation 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. Cancer Res; 72(14); 3593–606. ©2012 AACR.

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