ZNF217 Is a Marker of Poor Prognosis in Breast Cancer That Drives Epithelial–Mesenchymal Transition and Invasion

Abstract

The Kr€ uppel-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-b-activated Smad signaling pathway was identified as a major driver of ZNF217-induced EMT. In addition, a TGF-b autocrine loop sustained activation of the TGF-b pathway in ZNF217-overexpressing mammary epithelial cells, most likely because of ZNF217-mediated direct upregulation of TGFB2 or TGFB3. Inhibition of the TGF-b 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-b signaling pathway may benefit the subset of patients whose tumors express high levels of ZNF217. Cancer Res; 72(14); 3593-606. Ó2012 AACR.

Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas

“…Further genes in the minimal differentiation set were ZNF217 , COL14A1 and DMRT2. ZNF217 is a marker of poor prognosis in breast cancer [65], COL14A1 is a candidate tumor-suppressor gene frequently methylated in renal cell carcinomas [66] and the transcription factor DMRT2 is downregulated in clear-cell renal-cell carcinomas [67]. …”

Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population

“…Many previous investigations focused on the epithelial mesenchymal transition of breast cancer, which was believed to be one of the important mechanisms of tumor metastasis (Chakrabarti et al, 2012;Guttilla et al, 2012;Vendrell et al, 2012). It is noteworthy that HA and HRH4 were reported to play very important roles in epithelial mesenchymal transition and metastasis of cancer cells (Meng et al, 2011).…”

New Insights into DNA Recognition by Zinc Fingers Revealed by Structural Analysis of the Oncoprotein ZNF217

“…High levels of ZNF217 are associated with a poor prognosis in breast cancer (31), and overexpression of the ZNF217 gene in human mammary epithelial cells immortalizes those cells (32). ZNF217 contains seven predicted classical ZFs, found in two clusters in the N-terminal half of the protein.…”