title: 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.
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.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Montorsi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Guizzetti
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Alecci
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Caporali
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Martello
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Claudio Giacinto
authors.initials: CG
authors.lastname: Atene
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Parenti
authors.affiliation: Centre for Integrative Biology (CIBIO), University of Trento, Povo (Trento), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pizzini
authors.affiliation: Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bortoluzzi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Alexis
authors.initials: A
authors.lastname: Grande
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Zanocco-Marani
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C544162:MACC1 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051816:Tristetraprolin; C486307:ZEB1 protein, human; C497552:ZFP36 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin
keywords: ZFP36; colon cancer; epithelial mesenchymal transition; tristetraprolin; β-catenin