ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression

Payam Shahi; Chih Yang Wang; Devon A. Lawson; Euan M. Slorach; Angela Lu; Ying Yu; Ming Derg Lai; Hugo Gonzalez Velozo; Zena Werb

doi:10.1073/pnas.1701690114

ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression

Payam Shahi, Chih Yang Wang, Devon A. Lawson, Euan M. Slorach, Angela Lu, Ying Yu, Ming Derg Lai, Hugo Gonzalez Velozo, Zena Werb

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for downregulation of GATA3 via ZPO2. Through this modulation of GATA3 activity, ZPO2 promotes aggressive breast cancer development. Our data provide insight into a mechanism of GATA3 regulation, and identify ZPO2 as a possible candidate gene for future diagnostic and therapeutic strategies.

Original language	English
Pages (from-to)	3169-3174
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	12
DOIs	https://doi.org/10.1073/pnas.1701690114
Publication status	Published - Mar 21 2017
Externally published	Yes

Keywords

Breast cancer
GATA3
Tumor metastasis
ZBTB32
ZNF503/ZPO2

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.1701690114

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@article{99d975ef8706492f8cdfff122830bac5,

title = "ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression",

abstract = "The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for downregulation of GATA3 via ZPO2. Through this modulation of GATA3 activity, ZPO2 promotes aggressive breast cancer development. Our data provide insight into a mechanism of GATA3 regulation, and identify ZPO2 as a possible candidate gene for future diagnostic and therapeutic strategies.",

keywords = "Breast cancer, GATA3, Tumor metastasis, ZBTB32, ZNF503/ZPO2",

author = "Payam Shahi and Wang, {Chih Yang} and Lawson, {Devon A.} and Slorach, {Euan M.} and Angela Lu and Ying Yu and Lai, {Ming Derg} and Velozo, {Hugo Gonzalez} and Zena Werb",

note = "Funding Information: We thank Dr. I. Cheng Ho for the Zbtb32 construct; Dr. Hope Rugo (University of California, San Francisco) for the donation of tumor samples; and Vicki Plaks, Amy-Jo Casbon, Caroline Bonnans, Kai Kessenbrock, Ken Takai, and Elena Atamanuic for their support and intellectual discussions. This research was funded by National Cancer Institute Grants R01 CA180039 and R01 CA190851 (to Z.W.), and Traineeship T32 CA108462 (to P.S.). This work was supported by Taiwan Ministry of Science and Technology Grant 104-2917-I-006-002 (to C.W.), US Department of Defense Congressionally Directed Medical Research Program Postdoctoral Fellowship 11-1-0742 (to D.A.L.), and a Becas Chile Scholarship (H.G.V.).",

year = "2017",

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doi = "10.1073/pnas.1701690114",

language = "English",

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T1 - ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression

AU - Shahi, Payam

AU - Wang, Chih Yang

AU - Lawson, Devon A.

AU - Slorach, Euan M.

AU - Lu, Angela

AU - Yu, Ying

AU - Lai, Ming Derg

AU - Velozo, Hugo Gonzalez

AU - Werb, Zena

N1 - Funding Information: We thank Dr. I. Cheng Ho for the Zbtb32 construct; Dr. Hope Rugo (University of California, San Francisco) for the donation of tumor samples; and Vicki Plaks, Amy-Jo Casbon, Caroline Bonnans, Kai Kessenbrock, Ken Takai, and Elena Atamanuic for their support and intellectual discussions. This research was funded by National Cancer Institute Grants R01 CA180039 and R01 CA190851 (to Z.W.), and Traineeship T32 CA108462 (to P.S.). This work was supported by Taiwan Ministry of Science and Technology Grant 104-2917-I-006-002 (to C.W.), US Department of Defense Congressionally Directed Medical Research Program Postdoctoral Fellowship 11-1-0742 (to D.A.L.), and a Becas Chile Scholarship (H.G.V.).

PY - 2017/3/21

Y1 - 2017/3/21

N2 - The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for downregulation of GATA3 via ZPO2. Through this modulation of GATA3 activity, ZPO2 promotes aggressive breast cancer development. Our data provide insight into a mechanism of GATA3 regulation, and identify ZPO2 as a possible candidate gene for future diagnostic and therapeutic strategies.

AB - The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for downregulation of GATA3 via ZPO2. Through this modulation of GATA3 activity, ZPO2 promotes aggressive breast cancer development. Our data provide insight into a mechanism of GATA3 regulation, and identify ZPO2 as a possible candidate gene for future diagnostic and therapeutic strategies.

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ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression

Abstract

Keywords

ASJC Scopus subject areas

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