The transcriptional repressor ZNF503/Zeppo2 promotes mammary epithelial cell proliferation and enhances cell invasion

Payam Shahi, Euan M. Slorach, Chih Yang Wang, Jonathan Chou, Angela Lu, Aline Ruderisch, Zena Werb

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The NET (nocA, Nlz, elB, TLP-1) subfamilyofzinc finger proteins is an important mediator during developmental processes. The evolutionary conserved zinc finger protein ZNF503/Zeppo2 (zinc finger elbow-related proline domain protein 2, Zpo2) plays critical roles during embryogenesis. We found that Zpo2 is expressed in adult tissue and examined its function. We found that ZPO2 is a nuclearly targeted transcriptional repressor that is expressed in mammary epithelial cells. Elevated Zpo2 levels increase mammary epithelial cell proliferation. Zpo2 promotes cellular invasion through down-regulation of E-cadherin and regulates the invasive phenotype ina RAC1-dependent manner. We detect elevated Zpo2 expression during breast cancer progression in a MMTV-PyMT transgenic mouse model. Tumor transplant experiments indicated that overexpression of Zpo2 in MMTV-PyMT mammary tumor cell lines enhances lung metastasis. Our findings suggest that Zpo2 plays a significant role in mammary gland homeostasis and that deregulation of Zpo2 may promote breast cancer development.

Original languageEnglish
Pages (from-to)3803-3813
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number6
DOIs
Publication statusPublished - Feb 6 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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