RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer

Ji Hoon Oh, Ji Yeon Lee, Sungsook Yu, Yejin Cho, Sumin Hur, Ki Taek Nam, Myoung Hee Kim

Research output: Contribution to journalArticle

Abstract

Breast cancer metastasis accounts for most of the deaths from breast cancer. Since epithelial-mesenchymal transition (EMT) plays an important role in promoting metastasis of cancer, many mechanisms regarding EMT have been studied. We previously showed that Ribonucleic acid export 1 (RAE1) is dysregulated in breast cancer and its overexpression leads to aggressive breast cancer phenotypes by inducing EMT. Here, we evaluated the functional capacity of RAE1 in breast cancer metastasis by using a three-dimensional (3D) culture system and xenograft models. Furthermore, to investigate the mechanisms of RAE1-driven EMT, in vitro studies were carried out. The induction of EMT with RAE1-overexpression was confirmed under the 3D culture system and in vivo system. Importantly, RAE1 mediates upregulation of an EMT marker ZEB1, by binding to the promoter region of ZEB1. Knockdown of ZEB1 in RAE1-overexpressing cells suppressed invasive and migratory behaviors, accompanied by an increase in epithelial and a decrease in mesenchymal markers. Taken together, these data demonstrate that RAE1 contributes to breast cancer metastasis by regulating a key EMT-inducing factor ZEB1 expression, suggesting its potential as a therapeutic target.

Original languageEnglish
Article number2977
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Fingerprint

Epithelial-Mesenchymal Transition
RNA
Breast Neoplasms
Neoplasm Metastasis
Heterografts
Genetic Promoter Regions
Up-Regulation
Phenotype
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

Cite this

Oh, Ji Hoon ; Lee, Ji Yeon ; Yu, Sungsook ; Cho, Yejin ; Hur, Sumin ; Nam, Ki Taek ; Kim, Myoung Hee. / RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer. In: Scientific reports. 2019 ; Vol. 9, No. 1.
@article{8349dc4507f1447685f75ab6b6567907,
title = "RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer",
abstract = "Breast cancer metastasis accounts for most of the deaths from breast cancer. Since epithelial-mesenchymal transition (EMT) plays an important role in promoting metastasis of cancer, many mechanisms regarding EMT have been studied. We previously showed that Ribonucleic acid export 1 (RAE1) is dysregulated in breast cancer and its overexpression leads to aggressive breast cancer phenotypes by inducing EMT. Here, we evaluated the functional capacity of RAE1 in breast cancer metastasis by using a three-dimensional (3D) culture system and xenograft models. Furthermore, to investigate the mechanisms of RAE1-driven EMT, in vitro studies were carried out. The induction of EMT with RAE1-overexpression was confirmed under the 3D culture system and in vivo system. Importantly, RAE1 mediates upregulation of an EMT marker ZEB1, by binding to the promoter region of ZEB1. Knockdown of ZEB1 in RAE1-overexpressing cells suppressed invasive and migratory behaviors, accompanied by an increase in epithelial and a decrease in mesenchymal markers. Taken together, these data demonstrate that RAE1 contributes to breast cancer metastasis by regulating a key EMT-inducing factor ZEB1 expression, suggesting its potential as a therapeutic target.",
author = "Oh, {Ji Hoon} and Lee, {Ji Yeon} and Sungsook Yu and Yejin Cho and Sumin Hur and Nam, {Ki Taek} and Kim, {Myoung Hee}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-39574-8",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer. / Oh, Ji Hoon; Lee, Ji Yeon; Yu, Sungsook; Cho, Yejin; Hur, Sumin; Nam, Ki Taek; Kim, Myoung Hee.

In: Scientific reports, Vol. 9, No. 1, 2977, 01.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer

AU - Oh, Ji Hoon

AU - Lee, Ji Yeon

AU - Yu, Sungsook

AU - Cho, Yejin

AU - Hur, Sumin

AU - Nam, Ki Taek

AU - Kim, Myoung Hee

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Breast cancer metastasis accounts for most of the deaths from breast cancer. Since epithelial-mesenchymal transition (EMT) plays an important role in promoting metastasis of cancer, many mechanisms regarding EMT have been studied. We previously showed that Ribonucleic acid export 1 (RAE1) is dysregulated in breast cancer and its overexpression leads to aggressive breast cancer phenotypes by inducing EMT. Here, we evaluated the functional capacity of RAE1 in breast cancer metastasis by using a three-dimensional (3D) culture system and xenograft models. Furthermore, to investigate the mechanisms of RAE1-driven EMT, in vitro studies were carried out. The induction of EMT with RAE1-overexpression was confirmed under the 3D culture system and in vivo system. Importantly, RAE1 mediates upregulation of an EMT marker ZEB1, by binding to the promoter region of ZEB1. Knockdown of ZEB1 in RAE1-overexpressing cells suppressed invasive and migratory behaviors, accompanied by an increase in epithelial and a decrease in mesenchymal markers. Taken together, these data demonstrate that RAE1 contributes to breast cancer metastasis by regulating a key EMT-inducing factor ZEB1 expression, suggesting its potential as a therapeutic target.

AB - Breast cancer metastasis accounts for most of the deaths from breast cancer. Since epithelial-mesenchymal transition (EMT) plays an important role in promoting metastasis of cancer, many mechanisms regarding EMT have been studied. We previously showed that Ribonucleic acid export 1 (RAE1) is dysregulated in breast cancer and its overexpression leads to aggressive breast cancer phenotypes by inducing EMT. Here, we evaluated the functional capacity of RAE1 in breast cancer metastasis by using a three-dimensional (3D) culture system and xenograft models. Furthermore, to investigate the mechanisms of RAE1-driven EMT, in vitro studies were carried out. The induction of EMT with RAE1-overexpression was confirmed under the 3D culture system and in vivo system. Importantly, RAE1 mediates upregulation of an EMT marker ZEB1, by binding to the promoter region of ZEB1. Knockdown of ZEB1 in RAE1-overexpressing cells suppressed invasive and migratory behaviors, accompanied by an increase in epithelial and a decrease in mesenchymal markers. Taken together, these data demonstrate that RAE1 contributes to breast cancer metastasis by regulating a key EMT-inducing factor ZEB1 expression, suggesting its potential as a therapeutic target.

UR - http://www.scopus.com/inward/record.url?scp=85062271290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062271290&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-39574-8

DO - 10.1038/s41598-019-39574-8

M3 - Article

C2 - 30814639

AN - SCOPUS:85062271290

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 2977

ER -