Gavert Nancy, Ben-Ze'ev Avri
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
J Cell Biochem. 2007 Nov 1;102(4):820-8. doi: 10.1002/jcb.21505.
A coordinated integration of cell-cell adhesion and the control of gene expression is essential for the development of multicellular, differentiated organisms. beta-Catenin fulfils important regulatory functions in both cell-cell adhesion by linking cadherin adhesion receptors to the cytoskeleton, and also as a key element in the Wnt signaling pathway where it acts as cotranscriptional activator of target genes in the cell nucleus. Wnt signaling is involved in numerous aspects of embryonic development and in the control of tissue self-renewal in a variety of adult tissues. Hyperactivation of Wnt signaling, mostly by affecting beta-catenin functions, is a hallmark of colon cancer and of many other human cancers. In this prospect, we discuss studies pointing to the molecular mechanisms that govern the integration between cell-cell adhesion and gene expression, as reflected in the switches between these two functions of beta-catenin in colon cancer cells.
细胞间黏附与基因表达调控的协同整合对于多细胞分化生物体的发育至关重要。β-连环蛋白在细胞间黏附(通过将钙黏蛋白黏附受体与细胞骨架相连)以及Wnt信号通路中均发挥重要调节功能,在Wnt信号通路中它作为细胞核内靶基因的共转录激活因子。Wnt信号通路参与胚胎发育的多个方面以及多种成体组织中组织自我更新的调控。Wnt信号通路的过度激活,主要是通过影响β-连环蛋白的功能,是结肠癌及许多其他人类癌症的一个标志。在此展望中,我们讨论了一些研究,这些研究指向了控制细胞间黏附与基因表达整合的分子机制,这在结肠癌细胞中β-连环蛋白这两种功能的转换中得以体现。