title: Novel insights into Notum and glypicans regulation in colorectal cancer.
abstract: The connection between colorectal cancer (CRC) and Wnt signaling pathway activation is well known, but full elucidation of the underlying regulation of the Wnt/β-catenin pathway and its biological functions in CRC pathogenesis is still needed. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model has been used as an experimental platform able to mimic human sporadic CRC development with predictable timing. We performed genome-wide expression profiling of AOM/DSS-induced tumors and normal colon mucosa to identify potential novel CRC biomarkers. Remarkably, the enhanced expression of Notum, a conserved feedback antagonist of Wnt, was observed in tumors along with alterations in Glypican-1 and Glypican-3 levels. These findings were confirmed in a set of human CRC samples. Here, we provide the first demonstration of significant changes in Notum and glypicans gene expression during CRC development and present evidence to suggest them as potential new biomarkers of CRC pathogenesis.
authors.affiliation: Laboratory of Molecular Medicine and Biotechnology, Center of Integrated Research, Campus Bio-Medico University of Rome, 00128 Rome, Italy.|Laboratory of Molecular Pathology and Experimental Oncology, Institute of Translational Pharmacology, National Research Council (CNR), 00133 Rome, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: De Robertis
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Arigoni
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, 71013-San Giovanni Rotondo (FG), Italy.|Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Loiacono
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Riccardo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy.
authors.forename: Raffaele Adolfo
authors.initials: RA
authors.lastname: Calogero
authors.affiliation: Department of Medical Biology, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria.|Technological Centre of Emergency Medicine, 4000 Plovdiv, Bulgaria.
authors.forename: Yana
authors.initials: Y
authors.lastname: Feodorova
authors.affiliation: Department of General and Clinical Pathology, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria.
authors.forename: Dessislava
authors.initials: D
authors.lastname: Tashkova
authors.affiliation: Department of General and Clinical Pathology, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria.
authors.forename: Vesselin
authors.initials: V
authors.lastname: Belovejdov
authors.affiliation: Department of Medical Biology, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria.|Technological Centre of Emergency Medicine, 4000 Plovdiv, Bulgaria.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sarafian
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.affiliation: Laboratory of Molecular Medicine and Biotechnology, Center of Integrated Research, Campus Bio-Medico University of Rome, 00128 Rome, Italy.|Laboratory of Molecular Pathology and Experimental Oncology, Institute of Translational Pharmacology, National Research Council (CNR), 00133 Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Signori
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics*; D004950:Esterases / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D053673:Glypicans / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D053673:Glypicans; D004950:Esterases; C000596390:Notum protein, human; C000611122:Notum protein, mouse
keywords: Notum; WNT-pathway; colorectal carcinogenesis; glypicans; predictable animal models