Regulation of NF-kB by the ZO-1/ZONAB pathway

上皮是描绘我们的组织和器官的连续的细胞层。上皮细胞的完整性对于我们的器官的正常运作和保护我们免受环境的伤害是很重要的。例如，皮肤或肠道衬里等上皮层的破裂可能会导致严重的感染。单个上皮细胞通过分子复合体相互作用，分子复合体不仅介导黏附，而且还起到传感器的作用，将有关环境的信息，如邻近细胞的存在或不存在，传递到细胞内部。这些传感器对调节细胞行为很重要，因为它们告诉细胞什么时候分裂，什么时候停止生长。例如，如果上皮细胞受损，细胞分裂并迁移以修复孔洞，直到它们到达邻近细胞，并形成新的粘连复合体。因此，这些感觉机制的缺陷会导致癌症等严重疾病。许多炎症性疾病会影响这些黏附分子复合体的功能特性。这些疾病可由细菌和病毒以及过敏原引起，或由我们自身的身体防御系统引起，通常直接涉及粘附性复合体的成分。例如，一种导致胃癌的细菌将分子注入上皮细胞，刺激黏附复合体的解离。这种感染还会引起细胞炎症反应，帮助我们的身体应对它们。然而，这些细胞反应可能会失控并造成损害。在这里，我们将重点放在一个新的分子机制上，通过它，上皮细胞中的黏附复合体可以调节细胞的炎症反应。我们建议研究分子机制，并确定它是如何在两种人类疾病模型中受到影响的。一个模型是基于上述导致胃癌的细菌，另一个模型是从结肠癌和前列腺癌中分离出来的细胞。了解黏附复合体是如何引导炎症反应的，将有助于我们设计针对上述疾病的新疗法。

Epithelia are continuous layers of cells that delineate our tissues and organs. The integrity of epithelia is important for our organs to function normally and to protect us from our environment. For example, breaches in epithelial layers such as the skin or in the lining of the intestine can lead to serious infections. Individual epithelial cells interact with each other via molecular complexes that mediate adhesion but also function as sensors that transmit information about the environment, such as the presence or absence of neighbouring cells, to the cell interior. These sensors are important for the regulation of cell behaviour as they tell cells when to divide and when to stop to grow. If an epithelium is damaged, for example, cells divide and migrate to repair holes until they reach their neighbours and can form new adhesive complexes. Therefore, defects in these sensory mechanisms lead to severe diseases such as cancer. Many inflammatory diseases affect the functional properties of these adhesive molecular complexes. These diseases can be caused by bacteria and viruses, as well as allergens or by our own body defence system and often directly involve components of adhesive complexes. For example, a bacterium that causes gastric cancer injects molecules into epithelial cells that stimulate dissociation of adhesive complexes. Such infections also cause a cellular inflammatory response that helps our body to deal with them. However, these cellular responses can get out of control and cause damage. Here we focus on a new molecular mechanism by which adhesive complexes in epithelial cells can regulate the cellular inflammatory response. We propose to study the molecular mechanism and to determine how it is affected in two models of human disease. One model is based on the mentioned bacterium that causes gastric cancer and the other on cells isolated from colon and prostate cancers. Understanding how adhesive complexes guide the inflammatory response will help us to design new therapies for the above-mentioned diseases.