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

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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.