Cross-talk between Ajuba and Rac signalling in the stabilization of cadherin adhesion

细胞-细胞黏附是不同类型细胞生命中的关键事件，对于它们组织成更高级的结构如血管、肺、皮肤、肌肉等是必不可少的。相反，在细菌感染后发现细胞-细胞接触的去调节，可能会愈合或启动肿瘤的侵袭。我们感兴趣的是了解细胞如何控制它们与邻居粘合的能力，而不是分散到周围组织中。我们确定了一种名为Ajuba的分子，它在加强细胞间黏附方面起着关键作用：在没有Ajuba的情况下，细胞间的聚集大大减少。我们意想不到的发现是，Ajuba可以操纵小GTP酶Rac的功能，这是稳定细胞间接触所必需的。在这项提案中，我们将阐述Ajuba和RAC之间的串扰导致更强的细胞-细胞黏附的机制。了解Ajuba/RAC稳定连接的机制将突出潜在的干预肿瘤细胞侵袭和转移的策略。采取适当的策略来阻止转移生长将对癌症患者的生活质量产生重要的影响。

Cell-cell adhesion is a key event in the life of different cell types and is essential for their organization into higher ordered structures such as blood vessels, lung, skin, muscle, etc. Conversely, de-regulation of cell-cell contacts is found following bacterial infection, would healing or initiation of tumour invasion. We are interested in understanding how cells control their ability to glue to their neighbours as opposed to scatter into surrounding tissues. We identified a molecule, Ajuba, which plays a key role to strengthen cell-cell adhesion: in the absence of Ajuba, cell-cell aggregation is greatly reduced. Our unexpected finding is that Ajuba can manipulate the function of the small GTPase Rac, which is required to stabilize cell-cell contacts. In this proposal, we will address the mechanisms via which crosstalk between Ajuba and Rac leads to stronger cell-cell adhesion. Understanding the mechanisms via which Ajuba/Rac stabilize junctions will highlight potential strategies to interfere with tumour cell invasion and metastasis. Suitable strategies to stall metastatic growth will have important implications for the quality of life of cancer patients.