Cargando…
Loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1
The mRNA-destabilizing protein ZFP36 has been previously described as a tumor suppressor whose expression is lost during colorectal cancer development. In order to evaluate its role in this disease, we restored ZFP36 expression in different cell contexts, showing that the presence of this protein im...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312301/ https://www.ncbi.nlm.nih.gov/pubmed/27463018 http://dx.doi.org/10.18632/oncotarget.10828 |
_version_ | 1782508179108659200 |
---|---|
author | Montorsi, Lucia Guizzetti, Filippo Alecci, Claudia Caporali, Andrea Martello, Andrea Atene, Claudio Giacinto Parenti, Sandra Pizzini, Silvia Zanovello, Paola Bortoluzzi, Stefania Ferrari, Sergio Grande, Alexis Zanocco-Marani, Tommaso |
author_facet | Montorsi, Lucia Guizzetti, Filippo Alecci, Claudia Caporali, Andrea Martello, Andrea Atene, Claudio Giacinto Parenti, Sandra Pizzini, Silvia Zanovello, Paola Bortoluzzi, Stefania Ferrari, Sergio Grande, Alexis Zanocco-Marani, Tommaso |
author_sort | Montorsi, Lucia |
collection | PubMed |
description | The mRNA-destabilizing protein ZFP36 has been previously described as a tumor suppressor whose expression is lost during colorectal cancer development. In order to evaluate its role in this disease, we restored ZFP36 expression in different cell contexts, showing that the presence of this protein impairs the epithelial-to-mesenchymal transition (EMT) and induces a higher susceptibility to anoikis. Consistently, we found that ZFP36 inhibits the expression of three key transcription factors involved in EMT: ZEB1, MACC1 and SOX9. Finally, we observed for the first time that its expression negatively correlates with the activity of Wnt/β-catenin pathway, which is constitutively activated in colorectal cancer. This evidence provides a clue on the mechanism leading to the loss of ZFP36 in CRC. |
format | Online Article Text |
id | pubmed-5312301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53123012017-03-06 Loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1 Montorsi, Lucia Guizzetti, Filippo Alecci, Claudia Caporali, Andrea Martello, Andrea Atene, Claudio Giacinto Parenti, Sandra Pizzini, Silvia Zanovello, Paola Bortoluzzi, Stefania Ferrari, Sergio Grande, Alexis Zanocco-Marani, Tommaso Oncotarget Research Paper The mRNA-destabilizing protein ZFP36 has been previously described as a tumor suppressor whose expression is lost during colorectal cancer development. In order to evaluate its role in this disease, we restored ZFP36 expression in different cell contexts, showing that the presence of this protein impairs the epithelial-to-mesenchymal transition (EMT) and induces a higher susceptibility to anoikis. Consistently, we found that ZFP36 inhibits the expression of three key transcription factors involved in EMT: ZEB1, MACC1 and SOX9. Finally, we observed for the first time that its expression negatively correlates with the activity of Wnt/β-catenin pathway, which is constitutively activated in colorectal cancer. This evidence provides a clue on the mechanism leading to the loss of ZFP36 in CRC. Impact Journals LLC 2016-07-24 /pmc/articles/PMC5312301/ /pubmed/27463018 http://dx.doi.org/10.18632/oncotarget.10828 Text en Copyright: © 2016 Montorsi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Montorsi, Lucia Guizzetti, Filippo Alecci, Claudia Caporali, Andrea Martello, Andrea Atene, Claudio Giacinto Parenti, Sandra Pizzini, Silvia Zanovello, Paola Bortoluzzi, Stefania Ferrari, Sergio Grande, Alexis Zanocco-Marani, Tommaso Loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1 |
title | Loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1 |
title_full | Loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1 |
title_fullStr | Loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1 |
title_full_unstemmed | Loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1 |
title_short | Loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1 |
title_sort | loss of zfp36 expression in colorectal cancer correlates to wnt/ β-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of zeb1, sox9 and macc1 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312301/ https://www.ncbi.nlm.nih.gov/pubmed/27463018 http://dx.doi.org/10.18632/oncotarget.10828 |
work_keys_str_mv | AT montorsilucia lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT guizzettifilippo lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT alecciclaudia lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT caporaliandrea lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT martelloandrea lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT ateneclaudiogiacinto lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT parentisandra lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT pizzinisilvia lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT zanovellopaola lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT bortoluzzistefania lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT ferrarisergio lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT grandealexis lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 AT zanoccomaranitommaso lossofzfp36expressionincolorectalcancercorrelatestowntbcateninactivityandenhancesepithelialtomesenchymaltransitionthroughupregulationofzeb1sox9andmacc1 |