Open AccessEmerging role of the β-catenin-PPARγ axis in the pathogenesis of colorectal cancer
Author(s) -
Lina Sabatino,
Massimo Pancione,
Carolina Votino,
Tommaso Colangelo,
Angelo Lupo,
Ettore Novellino,
Antonio Lavecchia,
Vittorio Colantuoni
Publication year - 2014
Publication title -
world journal of gastroenterology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.427
H-Index - 155
eISSN - 2219-2840
pISSN - 1007-9327
DOI - 10.3748/wjg.v20.i23.7137
Subject(s) - wnt signaling pathway , catenin , cancer research , colorectal cancer , carcinogenesis , crosstalk , epigenetics , biology , signal transduction , peroxisome proliferator activated receptor , bioinformatics , cancer , medicine , microbiology and biotechnology , receptor , genetics , gene , physics , optics
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.