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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
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