Novel insights into Notum and glypicans regulation in colorectal cancer
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Mariangela De Robertis1,2, Maddalena Arigoni3, Luisa Loiacono4,5, Federica Riccardo3, Raffaele Adolfo Calogero3, Yana Feodorova6,7, Dessislava Tashkova8, Vesselin Belovejdov8, Victoria Sarafian6,7, Federica Cavallo3, Emanuela Signori1,2
1Laboratory of Molecular Medicine and Biotechnology, Center of Integrated Research, Campus Bio-Medico University of Rome, 00128 Rome, Italy
2Laboratory of Molecular Pathology and Experimental Oncology, Institute of Translational Pharmacology, National Research Council (CNR), 00133 Rome, Italy
3Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy
4Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, 71013-San Giovanni Rotondo (FG), Italy
5Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy
6Department of Medical Biology, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria
7Technological Centre of Emergency Medicine, 4000 Plovdiv, Bulgaria
8Department of General and Clinical Pathology, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria
Emanuela Signori, e-mail: [email protected]
Keywords: Notum, glypicans, colorectal carcinogenesis, predictable animal models, WNT-pathway
Received: June 25, 2015 Accepted: September 12, 2015 Published: October 20, 2015
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.
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