Najdi Rani, Holcombe Randall F, Waterman Marian L
Department of Microbiology and Molecular Genetics, University of California, Irvine.
J Carcinog. 2011 Mar 17;10:5. doi: 10.4103/1477-3163.78111.
Activation of the Wnt signaling pathway via mutation of the adenomatous polyposis coli gene (APC) is a critical event in the development of colon cancer. For colon carcinogenesis, however, constitutive signaling through the canonical Wnt pathway is not a singular event. Here we review how canonical Wnt signaling is modulated by intracellular LEF/TCF composition and location, the action of different Wnt ligands, and the secretion of Wnt inhibitory molecules. We also review the contributions of non-canonical Wnt signaling and other distinct pathways in the tumor micro environment that cross-talk to the canonical Wnt pathway and thereby influence colon cancer progression. These 'non-APC' aspects of Wnt signaling are considered in relation to the development of potential agents for the treatment of patients with colon cancer. Regulatory pathways that influence Wnt signaling highlight how it might be possible to design therapies that target a network of signals beyond that of APC and β-catenin.
通过腺瘤性息肉病大肠杆菌基因（APC）突变激活Wnt信号通路是结肠癌发生发展中的关键事件。然而，对于结肠癌的发生来说，通过经典Wnt途径的组成性信号传导并非单一事件。在此，我们综述了经典Wnt信号如何受到细胞内LEF/TCF组成和定位、不同Wnt配体的作用以及Wnt抑制分子分泌的调节。我们还综述了非经典Wnt信号以及肿瘤微环境中与经典Wnt途径相互作用从而影响结肠癌进展的其他不同途径的作用。Wnt信号的这些“非APC”方面与结肠癌患者潜在治疗药物的开发相关。影响Wnt信号的调节途径凸显了设计靶向APC和β-连环蛋白之外信号网络的疗法的可能性。
