E-cadherin-mediated cell-cell junctions play a prominent role in maintaining epithelial architecture. Their dysregulation in cancer can lead to the collapse of tumour epithelia and subsequent invasion and metastasis. Recent evidence suggests that, apart from modulating E-cadherin expression, cells are able to mobilise E-cadherin within their cell-cell junctions upon migration and invasion. We have developed new tools to assess the spatiotemporal dynamics of epithelial tumour cell-cell junctions to study the earliest stages of invasion and metastasis.
Methods:
Here, we have generated an E-cadherin-GFP mouse, which enables intravital quantification of E-cadherin clustering and mobility to provide insight into tumour cell-cell junction strength and integrity in intact tissues and tumours.
Results: We reveal that:
(1) E-cadherin mobility and clustering become de-regulated in invasive and metastatic tumours compared to healthy tissues and non-invasive pancreatic tumours.
(2) These subcellular aberrations in E-cadherin dynamics can be targeted with anti-invasive treatment to re-stabilise cell-cell junctions and to reduce cancer invasiveness.
Discussion: We suggest that these techniques can be used as:
(1) novel tools to fundamentally expand our understanding of cell-cell junction dynamics in vivo in native microenvironments
(2) novel pre-clinical drug-screening platform to predict cancer spread and to estimate the efficacy of anti-invasive treatment.