Janssens Nico, Janicot Michel, Perera Tim
Department of Biochemistry, University of Antwerp, Wilrijk, Belgium.
Invest New Drugs. 2006 Jul;24(4):263-80. doi: 10.1007/s10637-005-5199-4.
Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer's disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways.
我们目前对Wnt依赖信号通路的理解主要基于在多种模式生物中开展的研究，这些模式生物包括非洲爪蟾、黑腹果蝇、秀丽隐杆线虫和哺乳动物。这些研究清楚地表明，Wnt依赖信号通路在进化过程中是保守的，并在胚胎发育期间控制许多事件。Wnt通路已被证明可调节细胞增殖、形态、运动性以及细胞命运。在过去十年中，科学界对Wnt依赖信号通路的兴趣与日俱增，这得益于这些通路在广泛生理状况和疾病状态中的重要作用被记录在案。例如，已表明这些通路的不适当调节和激活与多种病理紊乱相关，包括癌症、视网膜病变、四肢发育不全以及骨和软骨疾病（如关节炎）。此外，Wnt依赖信号通路的几个组分似乎在诸如阿尔茨海默病、精神分裂症、双相情感障碍等疾病以及新兴的干细胞研究领域中发挥重要作用。在本综述中，我们希望对Wnt依赖信号通路的功能及其在肿瘤发生和癌症发展中的作用进行重点概述。我们还想提供有关这些通路中一些潜在药物靶点的信息，用于肿瘤学药物研发，并总结目前关于包括小分子抑制剂开发在内的方法的数据，这些方法已显示出对Wnt依赖信号通路有相关作用。
