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Novel insights into Notum and glypicans regulation in colorectal cancer

2015; Impact Journals LLC; Volume: 6; Issue: 38 Linguagem: Inglês

10.18632/oncotarget.5652

1949-2553

Mariangela De Robertis, Maddalena Arigoni, Luisa Loiacono, Federica Riccardo, Raffaele Calogero, Yana Feodorova, Dessislava Tashkova, Vesselin Belovejdov, Victoria Sarafian, Federica Cavallo, Emanuela Signori,

RNA Research and Splicing

// Mariangela De Robertis 1, 2 , Maddalena Arigoni 3 , Luisa Loiacono 4, 5 , Federica Riccardo 3 , Raffaele Adolfo Calogero 3 , Yana Feodorova 6, 7 , Dessislava Tashkova 8 , Vesselin Belovejdov 8 , Victoria Sarafian 6, 7 , Federica Cavallo 3 , Emanuela Signori 1, 2 1 Laboratory of Molecular Medicine and Biotechnology, Center of Integrated Research, Campus Bio-Medico University of Rome, 00128 Rome, Italy 2 Laboratory of Molecular Pathology and Experimental Oncology, Institute of Translational Pharmacology, National Research Council (CNR), 00133 Rome, Italy 3 Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy 4 Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, 71013-San Giovanni Rotondo (FG), Italy 5 Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy 6 Department of Medical Biology, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria 7 Technological Centre of Emergency Medicine, 4000 Plovdiv, Bulgaria 8 Department of General and Clinical Pathology, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria Correspondence to: Emanuela Signori, e-mail: emanuela.signori@ift.cnr.it Keywords: Notum, glypicans, colorectal carcinogenesis, predictable animal models, WNT-pathway Received: June 25, 2015 Accepted: September 12, 2015 Published: October 20, 2015 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.