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

Scientific Reports
Ji Hoon OhMyoung Hee Kim

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.

References

Sep 5, 2002·Nature Reviews. Drug Discovery·Andrew L Hopkins, Colin R Groom
Apr 15, 2004·Trends in Biochemical Sciences·Birthe FahrenkrogUeli Aebi
Apr 28, 2004·Breast Cancer Research and Treatment·Jong Bin KimMike J O'Hare
Aug 2, 2005·Nature Reviews. Cancer·Britta WeigeltLaura J van 't Veer
Feb 16, 2006·The Journal of Cell Biology·Darren J BakerJan M A van Deursen
Jun 6, 2007·Nature Reviews. Genetics·Asifa Akhtar, Susan M Gasser
Sep 13, 2008·Trends in Cell Biology·Maximiliano A D'Angelo, Martin W Hetzer
Jun 23, 2009·EMBO Reports·Maya Capelson, Martin W Hetzer
Jul 7, 2009·Seminars in Cell & Developmental Biology·Songli Xu, Maureen A Powers
Apr 14, 2010·Molecular Cell·Alwin Köhler, Ed Hurt
Sep 22, 2010·Gastroenterology·Ki Taek NamJames R Goldenring
Dec 24, 2010·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ozlem Darcansoy IşeriUfuk Gündüz
Jul 27, 2011·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Yinyin YuanFlorian Markowetz
Dec 14, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Henna V KuusistoDavid A Jans
Jan 3, 2012·Biochemical Pharmacology·Joel G TurnerDaniel M Sullivan
Jan 10, 2012·International Journal of Cell Biology·Masahiro KumetaKunio Takeyasu
Mar 14, 2013·Progress in Molecular Biology and Translational Science·Alexander Gheldof, Geert Berx
Apr 16, 2013·Trends in Cell Biology·Biljana Culjkovic-Kraljacic, Katherine L B Borden
Oct 22, 2013·Genes & Development·Jeff H Tsai, Jing Yang
Feb 25, 2014·Advances in Experimental Medicine and Biology·Dan N Simon, Michael P Rout
Feb 19, 2015·Genes & Development·Arkaitz Ibarra, Martin W Hetzer
Jan 29, 2016·Journal of Clinical Medicine·Yanyuan WuJaydutt V Vadgama
May 26, 2017·Acta Biochimica Et Biophysica Sinica·Ji Hoon OhMyoung Hee Kim
Jul 25, 2017·Trends in Cell Biology·Atsushi Satomura, Jason H Brickner
Aug 18, 2018·Biochemical and Biophysical Research Communications·Ji-Yeon LeeMyoung Hee Kim

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Citations

Dec 29, 2020·Biochemical and Biophysical Research Communications·Koki KatoRichard W Wong

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Methods Mentioned

BETA
xenograft
Confocal microscopy
ChIP
transfection
Fluorescence
PCR
immunoprecipitation
ChIP-PCR

Software Mentioned

JMP
Zen

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