Sugimura Ryohichi, Li Linheng
Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, Missouri 64110, USA.
Birth Defects Res C Embryo Today. 2010 Dec;90(4):243-56. doi: 10.1002/bdrc.20195.
Wnt signaling regulates many aspects of vertebrate development and adult stem cells. Deregulation of Wnt signaling causes development defect and cancer. The signaling is categorized in two pathways: canonical and noncanonical. Both pathways are initiated by Wnt ligands and Frizzled receptors. Canonical pathway leads to β-catenin:T-cell factor/lymphoid enhancer factor-mediated gene expression, which regulates proliferation and differentiation of cells. Noncanonical Wnt signaling is mediated by intracellular calcium ion and JNK. This signaling leads to NFAT, a key transcriptional factor regulating gene expression. In addition, β-catenin:T-cell factor/lymphoid enhancer factor-mediated gene expression is downregulated by CaMKII-TAK1-NLK. Cellular polarity and motility are the main outcomes of the signaling. During development, noncanonical Wnt signaling is required for tissue formation. Recent studies have shown that atypical cadherin Flamingo contributes to noncanonical Wnt signaling by directing the migration of cells. Also, noncanonical Wnt signaling is required for maintenance of adult stem cells. In the field of cancer research, noncanonical Wnt signaling has been considered a tumor suppressor; however, recent evidence has shown that the signaling also enhances cancer progression in the later stages of disease. In this review, we describe and discuss components of noncanonical Wnt signaling, diseases caused by deregulation of the signaling, regulation of adult stem cells by the signaling, and implications in cancer biology.
Wnt信号传导调控脊椎动物发育和成年干细胞的多个方面。Wnt信号传导失调会导致发育缺陷和癌症。该信号传导分为两条途径：经典途径和非经典途径。两条途径均由Wnt配体和卷曲受体启动。经典途径导致β-连环蛋白：T细胞因子/淋巴样增强因子介导的基因表达，从而调节细胞的增殖和分化。非经典Wnt信号传导由细胞内钙离子和JNK介导。该信号传导导致NFAT，一种调节基因表达的关键转录因子。此外，β-连环蛋白：T细胞因子/淋巴样增强因子介导的基因表达会被CaMKII-TAK1-NLK下调。细胞极性和运动性是该信号传导的主要结果。在发育过程中，非经典Wnt信号传导是组织形成所必需的。最近的研究表明，非典型钙黏蛋白Flamingo通过引导细胞迁移促进非经典Wnt信号传导。此外，非经典Wnt信号传导是维持成年干细胞所必需的。在癌症研究领域，非经典Wnt信号传导一直被认为是一种肿瘤抑制因子；然而，最近的证据表明，该信号传导在疾病后期也会促进癌症进展。在这篇综述中，我们描述并讨论了非经典Wnt信号传导的组成部分、信号传导失调引起的疾病、该信号传导对成年干细胞的调节以及在癌症生物学中的意义。
