Wnt signaling and colon carcinogenesis: beyond APC.
Wnt signaling and colon carcinogenesis: beyond APC.
复制标题
DOI：
10.4103/1477-3163.78111
复制
发表时间：
2011-03-17
影响因子：
--
通讯作者：
Waterman ML
中科院分区：
文献类型：
--
作者：
Najdi R;Holcombe RF;Waterman ML
通过结肠腺瘤性息肉病基因（APC）突变激活Wnt信号通路是结肠癌发展中的一个关键事件。然而，对于结肠癌发生，通过经典Wnt途径的组成性信号传导不是一个单一的事件。在这里，我们回顾了经典的Wnt信号是如何调制的细胞内LEF/TCF的组成和位置，不同的Wnt配体的作用，以及Wnt抑制分子的分泌。我们还回顾了非经典Wnt信号传导和肿瘤微环境中其他不同途径的贡献，这些途径与经典Wnt途径相互作用，从而影响结肠癌的进展。Wnt信号传导的这些“非APC”方面被认为与用于治疗结肠癌患者的潜在药物的开发有关。影响Wnt信号传导的调节途径强调了如何设计针对APC和β-连环蛋白以外的信号网络的疗法。
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.