Loss of ZFP36 expression in colorectal cancer correlates to wnt/ ß-catenin activity and enhances epithelial-to-mesenchymal transition through upregulation of ZEB1, SOX9 and MACC1

结直肠癌中 ZFP36 表达缺失与 wnt/β-catenin 活性相关,并通过上调 ZEB1、SOX9 和 MACC1 增强上皮-间质转化

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作者: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

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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