Institut Pasteur, CNRS URA 2582, Cell Polarity and Migration Group, Paris, France.
Cell Adh Migr. 2012 Jul-Aug;6(4):327-32. doi: 10.4161/cam.20855. Epub 2012 Jul 1.
Cancer cell dissemination away from the primary tumor and their ability to form metastases remain the major causes of death from cancer. Understanding the molecular mechanisms triggering this event could lead to the design of new cancer treatments. The establishment and the maintenance of tissue architecture depend on the coordination of cell behavior within this tissue. Cell-cell interactions must form adhesive structures between neighboring cells while remaining highly dynamic to allow and control tissue renewal or remodeling. Among intercellular junctions, cadherin-based adherens junctions mediate strong physical interactions and transmit information from the cell microenvironment to the cytoplasm. Disruption of these cell-cell contacts perturbs the polarity of epithelial tissues leading to their disorganization and ultimately to aggressive carcinomas. In non-epithelial tissues, the role of cadherins in the development of cancer is still debated. We recently found that downregulation of N-cadherin in malignant glioma-the most frequent primary brain tumor-results in cell polarization defects leading to abnormal motile behavior with increased cell speed and decreased persistence in directionality. Re-expression of N-cadherin in glioma cells restores cell polarity and limits glioma cell migration, providing a potential therapeutic tool for diffuse glioma.
癌细胞从原发性肿瘤扩散并形成转移仍然是癌症死亡的主要原因。了解引发这一事件的分子机制可能会导致新的癌症治疗方法的设计。组织架构的建立和维持依赖于组织内细胞行为的协调。细胞-细胞相互作用必须在相邻细胞之间形成粘附结构，同时保持高度动态，以允许和控制组织更新或重塑。在细胞间连接中，基于钙黏蛋白的黏附连接介导强物理相互作用，并将细胞微环境中的信息传递到细胞质。破坏这些细胞-细胞接触会破坏上皮组织的极性，导致其组织紊乱，并最终导致侵袭性癌。在非上皮组织中，钙黏蛋白在癌症发展中的作用仍存在争议。我们最近发现，恶性神经胶质瘤（最常见的原发性脑肿瘤）中 N-钙黏蛋白的下调导致细胞极化缺陷，导致细胞运动行为异常，细胞速度增加，方向上的持久性降低。N-钙黏蛋白在神经胶质瘤细胞中的重新表达恢复了细胞极性，并限制了神经胶质瘤细胞的迁移，为弥漫性神经胶质瘤提供了一种潜在的治疗工具。
