Laprise Patrick
Department of Molecular Biology, Medical Biochemistry and Pathology/Cancer Research Center, Laval University and CRCHUQ-Hôtel-Dieu de Québec, 9 McMahon, Québec, QC, Canada G1R 2J6.
J Biomed Biotechnol. 2011;2011:868217. doi: 10.1155/2011/868217. Epub 2011 Sep 6.
Defects in apical-basal polarity regulation are associated with tissue overgrowth and tumorogenesis, yet the molecular mechanisms linking epithelial polarity regulators to hyperplasia or neoplasia remain elusive. In addition, exploration of the expression and function of the full complement of proteins required for the polarized architecture of epithelial cells in the context of cancer is awaited. This paper provides an overview of recent studies performed on Drosophila and vertebrates showing that apical polarity proteins of the Crumbs family act to repress tissue growth and epithelial to mesenchymal transition. Thus, these proteins emerge as potential tumor suppressors. Interestingly, analysis of the molecular function of Crumbs proteins reveals a function for these polarity regulators in junctional complexes stability and control of signaling pathways regulating proliferation and apoptosis. Thereby, these studies provide a molecular basis explaining how regulation of epithelial polarity is coupled to tumorogenesis.
顶端-基底端极性调控缺陷与组织过度生长和肿瘤发生相关,但将上皮极性调节因子与增生或肿瘤形成联系起来的分子机制仍不清楚。此外,在癌症背景下对上皮细胞极性结构所需的全套蛋白质的表达和功能进行探索仍有待开展。本文概述了近期在果蝇和脊椎动物上进行的研究,这些研究表明,Crumb家族的顶端极性蛋白具有抑制组织生长和上皮-间质转化的作用。因此,这些蛋白成为潜在的肿瘤抑制因子。有趣的是,对Crumb蛋白分子功能的分析揭示了这些极性调节因子在连接复合体稳定性以及调控增殖和凋亡的信号通路控制方面的作用。由此,这些研究提供了一个分子基础,解释了上皮极性调节如何与肿瘤发生相关联。