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emerging role of the β-catenin-PPARγ axis in the pathogenesis of colorectal cancer

World Journal of Gastroenterology 2014年第23期20卷 7137-7151页

作者： Lina Sabatino Massimo Pancione Carolina Votino tommaso colangelo Angelo Lupo Ettore Novellino Antonio Lavecchia Vittorio Colantuoni Department of Sciences and Technologies University of Sannio Department of Pharmacy "Drug Discovery" LaboratoryUniversity of Naples "Federico Ⅱ"80131 NaplesItaly

Multiple lines of evidence indicate that Wnt/β-catenin signaling plays a fundamental role in colorectal cancer (CRC) initiation and progression. Recent genome-wide data have confirmed that in CRC this pathway is one of the most frequently modified by genetic or epigenetic alterations affecting almost 90% of Wnt/β-catenin gene members. A major challenge is thus learning how the corrupted coordination of this pathway is tied to other signalings to enhance cell growth. Peroxisome proliferator activated receptor γ (PPARγ) is emerging as a growth-limiting and differentiation-promoting factor. In tumorigenesis it exerts a tumor suppressor role and is potentially linked with the Wnt/β-catenin pathway. Based on these results, the identification of new selective PPARγ modulators with inhibitory effects on the Wnt/β-catenin pathway is becoming an interesting perspective. Should, in fact, these molecules display such properties, new research avenues would be opened aimed at developing new molecular targeted drugs. Herein, we review the basic principles and present new hypotheses underlying the crosstalk between Wnt/β-catenin and PPARγ signaling. Furthermore, we discuss the advances in our understanding as to how their altered regulation can culminate in colon cancer and the efforts aimed at designing novel PPARγ agonists endowed with Wnt/β-catenin inhibitory effects to be used as therapeutic and/or preventive agents.

关键词： Colorectal cancer Wnt/β -catenin pathway Peroxisome proliferator-activated receptor γ Genomic instability Peroxisome proliferator activated receptor γ ligands

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