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

被引：110

作者：

Vendrell, Julie A. ^{[1
,2
]}

Thollet, Aurelie ^{[1
,2
]}

Nguyen, Nhan T. ^{[1
,2
]}

Ghayad, Sandra E. ^{[1
,2
]}

Vinot, Stephanie ^{[5
]}

Bieche, Ivan ^{[6
]}

Grisard, Evelyne ^{[1
,2
]}

Josserand, Veronique ^{[7
,8
]}

Coll, Jean-Luc ^{[7
,8
]}

Roux, Pierre ^{[5
]}

Corbo, Laura ^{[2
]}

Treilleux, Isabelle ^{[2
,3
]}

Rimokh, Ruth ^{[2
]}

Cohen, Pascale A. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Lyon 1, Fac Pharm Lyon, ISPB, ISPBL, F-69008 Lyon, France

[2] Ctr Rech Cancerol Lyon, CNRS UMR5286, U1052, INSERM, Lyon, France

[3] Ctr Leon Berard, Lyon, France

[4] ProfileXpert, SFR Lyon Est, Lyon, France

[5] Univ Montpellier 2, CRBM CNRS, UMR5237, IFR 122, Montpellier, France

[6] Hop Rene Huguenin, Inst Curie, Lab Oncogenet, St Cloud, France

[7] INSERM, U823, Grenoble, France

[8] Univ Grenoble 1, Inst Albert Bonniot, Grenoble, France

来源：

CANCER RESEARCH | 2012年 / 72卷 / 14期

关键词：

ENDOCRINE THERAPY RESISTANCE; TGF-BETA; ONCOGENIC TRANSFORMATION; IN-VITRO; CELLS; EXPRESSION; GENES; IDENTIFICATION; 20Q13; RECOGNITION;

D O I：

10.1158/0008-5472.CAN-11-3095

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The Kruppel-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-beta-activated Smad signaling pathway was identified as a major driver of ZNF217-induced EMT. In addition, a TGF-beta autocrine loop sustained activation of the TGF-beta pathway in ZNF217-overexpressing mammary epithelial cells, most likely because of ZNF217-mediated direct upregulation of TGFB2 or TGFB3. Inhibition of the TGF-beta 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-beta signaling pathway may benefit the subset of patients whose tumors express high levels of ZNF217. Cancer Res; 72(14); 3593-606. (C)2012 AACR.

引用

页码：3593 / 3606

页数：14

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