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

16 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

Fingerprint

Cell proliferation
Breast
Epithelial Cells
Zinc Fingers
Cell Proliferation
Breast Neoplasms
Zinc
Tumors
Transplants
Proteins
Deregulation
Cadherins
Human Mammary Glands
Elbow
Tumor Cell Line
Proline
Transgenic Mice
Fingers
Embryonic Development
Homeostasis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The transcriptional repressor ZNF503/Zeppo2 promotes mammary epithelial cell proliferation and enhances cell invasion. / Shahi, Payam; Slorach, Euan M.; Wang, Chih Yang; Chou, Jonathan; Lu, Angela; Ruderisch, Aline; Werb, Zena.

In: Journal of Biological Chemistry, Vol. 290, No. 6, 06.02.2015, p. 3803-3813.

Research output: Contribution to journalArticle

Shahi, Payam ; Slorach, Euan M. ; Wang, Chih Yang ; Chou, Jonathan ; Lu, Angela ; Ruderisch, Aline ; Werb, Zena. / The transcriptional repressor ZNF503/Zeppo2 promotes mammary epithelial cell proliferation and enhances cell invasion. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 6. pp. 3803-3813.
@article{1442454473764fdcbcf028652177c766,
title = "The transcriptional repressor ZNF503/Zeppo2 promotes mammary epithelial cell proliferation and enhances cell invasion",
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.",
author = "Payam Shahi and Slorach, {Euan M.} and Wang, {Chih Yang} and Jonathan Chou and Angela Lu and Aline Ruderisch and Zena Werb",
year = "2015",
month = "2",
day = "6",
doi = "10.1074/jbc.M114.611202",
language = "English",
volume = "290",
pages = "3803--3813",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "6",

}

TY - JOUR

T1 - The transcriptional repressor ZNF503/Zeppo2 promotes mammary epithelial cell proliferation and enhances cell invasion

AU - Shahi, Payam

AU - Slorach, Euan M.

AU - Wang, Chih Yang

AU - Chou, Jonathan

AU - Lu, Angela

AU - Ruderisch, Aline

AU - Werb, Zena

PY - 2015/2/6

Y1 - 2015/2/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84922369643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922369643&partnerID=8YFLogxK

U2 - 10.1074/jbc.M114.611202

DO - 10.1074/jbc.M114.611202

M3 - Article

C2 - 25538248

AN - SCOPUS:84922369643

VL - 290

SP - 3803

EP - 3813

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 6

ER -