The Transcription Factor <i>Elf3</i> Is Essential for a Successful Mesenchymal to Epithelial Transition

The epithelial to mesenchymal transition (EMT) and the mesenchymal to epithelial transition (MET) are two critical biological processes that are involved in both physiological events such as embryogenesis and development and also pathological events such as tumorigenesis. They present with dramatic...

Full description

Bibliographic Details
Main Authors: Burcu Sengez, Ilkin Aygün, Huma Shehwana, Neslihan Toyran, Sanem Tercan Avci, Ozlen Konu, Marc P. Stemmler, Hani Alotaibi
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/8/858
_version_ 1827835358131257344
author Burcu Sengez
Ilkin Aygün
Huma Shehwana
Neslihan Toyran
Sanem Tercan Avci
Ozlen Konu
Marc P. Stemmler
Hani Alotaibi
author_facet Burcu Sengez
Ilkin Aygün
Huma Shehwana
Neslihan Toyran
Sanem Tercan Avci
Ozlen Konu
Marc P. Stemmler
Hani Alotaibi
author_sort Burcu Sengez
collection DOAJ
description The epithelial to mesenchymal transition (EMT) and the mesenchymal to epithelial transition (MET) are two critical biological processes that are involved in both physiological events such as embryogenesis and development and also pathological events such as tumorigenesis. They present with dramatic changes in cellular morphology and gene expression exhibiting acute changes in E-cadherin expression. Despite the comprehensive understanding of EMT, the regulation of MET is far from being understood. To find novel regulators of MET, we hypothesized that such factors would correlate with <i>Cdh1</i> expression. Bioinformatics examination of several expression profiles suggested <i>Elf3</i> as a strong candidate. Depletion of <i>Elf3</i> at the onset of MET severely impaired the progression to the epithelial state. This MET defect was explained, in part, by the absence of E-cadherin at the plasma membrane. Moreover, during MET, ELF3 interacts with the <i>Grhl3</i> promoter and activates its expression. Our findings present novel insights into the regulation of MET and reveal ELF3 as an indispensable guardian of the epithelial state. A better understanding of MET will, eventually, lead to better management of metastatic cancers.
first_indexed 2024-03-12T06:07:25Z
format Article
id doaj.art-1e73693444464b47b4435e4f8d0cf6af
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-12T06:07:25Z
publishDate 2019-08-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj.art-1e73693444464b47b4435e4f8d0cf6af2023-09-03T03:26:14ZengMDPI AGCells2073-44092019-08-018885810.3390/cells8080858cells8080858The Transcription Factor <i>Elf3</i> Is Essential for a Successful Mesenchymal to Epithelial TransitionBurcu Sengez0Ilkin Aygün1Huma Shehwana2Neslihan Toyran3Sanem Tercan Avci4Ozlen Konu5Marc P. Stemmler6Hani Alotaibi7Izmir Biomedicine and Genome Center, 35340 Izmir, TurkeyIzmir International Biomedicine and Genome Institute, Dokuz Eylül University, 35340 Izmir, TurkeyDepartment of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, PakistanVocational School of Health Services, Dokuz Eylül University, 35340 Izmir, TurkeyIzmir Biomedicine and Genome Center, 35340 Izmir, TurkeyDepartment of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, TurkeyDepartment of Experimental Medicine 1, Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, GermanyIzmir Biomedicine and Genome Center, 35340 Izmir, TurkeyThe epithelial to mesenchymal transition (EMT) and the mesenchymal to epithelial transition (MET) are two critical biological processes that are involved in both physiological events such as embryogenesis and development and also pathological events such as tumorigenesis. They present with dramatic changes in cellular morphology and gene expression exhibiting acute changes in E-cadherin expression. Despite the comprehensive understanding of EMT, the regulation of MET is far from being understood. To find novel regulators of MET, we hypothesized that such factors would correlate with <i>Cdh1</i> expression. Bioinformatics examination of several expression profiles suggested <i>Elf3</i> as a strong candidate. Depletion of <i>Elf3</i> at the onset of MET severely impaired the progression to the epithelial state. This MET defect was explained, in part, by the absence of E-cadherin at the plasma membrane. Moreover, during MET, ELF3 interacts with the <i>Grhl3</i> promoter and activates its expression. Our findings present novel insights into the regulation of MET and reveal ELF3 as an indispensable guardian of the epithelial state. A better understanding of MET will, eventually, lead to better management of metastatic cancers.https://www.mdpi.com/2073-4409/8/8/858mesenchymal to epithelial transition<i>Elf3</i><i>Grhl3</i>Cadherins
spellingShingle Burcu Sengez
Ilkin Aygün
Huma Shehwana
Neslihan Toyran
Sanem Tercan Avci
Ozlen Konu
Marc P. Stemmler
Hani Alotaibi
The Transcription Factor <i>Elf3</i> Is Essential for a Successful Mesenchymal to Epithelial Transition
Cells
mesenchymal to epithelial transition
<i>Elf3</i>
<i>Grhl3</i>
Cadherins
title The Transcription Factor <i>Elf3</i> Is Essential for a Successful Mesenchymal to Epithelial Transition
title_full The Transcription Factor <i>Elf3</i> Is Essential for a Successful Mesenchymal to Epithelial Transition
title_fullStr The Transcription Factor <i>Elf3</i> Is Essential for a Successful Mesenchymal to Epithelial Transition
title_full_unstemmed The Transcription Factor <i>Elf3</i> Is Essential for a Successful Mesenchymal to Epithelial Transition
title_short The Transcription Factor <i>Elf3</i> Is Essential for a Successful Mesenchymal to Epithelial Transition
title_sort transcription factor i elf3 i is essential for a successful mesenchymal to epithelial transition
topic mesenchymal to epithelial transition
<i>Elf3</i>
<i>Grhl3</i>
Cadherins
url https://www.mdpi.com/2073-4409/8/8/858
work_keys_str_mv AT burcusengez thetranscriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT ilkinaygun thetranscriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT humashehwana thetranscriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT neslihantoyran thetranscriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT sanemtercanavci thetranscriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT ozlenkonu thetranscriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT marcpstemmler thetranscriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT hanialotaibi thetranscriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT burcusengez transcriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT ilkinaygun transcriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT humashehwana transcriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT neslihantoyran transcriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT sanemtercanavci transcriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT ozlenkonu transcriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT marcpstemmler transcriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition
AT hanialotaibi transcriptionfactorielf3iisessentialforasuccessfulmesenchymaltoepithelialtransition