Oncotarget

Research Papers:

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

Lucia Montorsi, Filippo Guizzetti, Claudia Alecci, Andrea Caporali, Andrea Martello, Claudio Giacinto Atene, Sandra Parenti, Silvia Pizzini, Paola Zanovello, Stefania Bortoluzzi, Sergio Ferrari, Alexis Grande, Tommaso Zanocco-Marani _

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Oncotarget. 2016; 7:59144-59157. https://doi.org/10.18632/oncotarget.10828

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Abstract

Lucia Montorsi1, Filippo Guizzetti1, Claudia Alecci1, Andrea Caporali2, Andrea Martello2, Claudio Giacinto Atene1, Sandra Parenti1, Silvia Pizzini5, Paola Zanovello4, Stefania Bortoluzzi3, Sergio Ferrari1, Alexis Grande1,*, Tommaso Zanocco-Marani1,*

1Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy

2University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK

3Department of Molecular Medicine, University of Padova, Padova, Italy

4Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy

5Centre for Integrative Biology (CIBIO), University of Trento, Povo (Trento), Italy

*These authors contributed equally to this work

Correspondence to:

Tommaso Zanocco-Marani, email: zanocco@unimore.it

Keywords: ZFP36, tristetraprolin, colon cancer, β-catenin, epithelial mesenchymal transition

Received: March 21, 2016     Accepted: July 09, 2016     Published: July 24, 2016

ABSTRACT

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.


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