Role of Dsg 3 in OSCC Cell Migration and Invasion

Objectives: Desmoglein 3 (Dsg3) is a member of desmosomal cadherins that plays a pivotal role in cell-cell adhesion and the maintenance of tissue integrity. Desmosomal cadherins have the ability of suppressing the invasiveness of cells in culture and the reduction of these proteins is frequently seen in cancer, the event that may facilitate tumour cell invasion and metastasis. Recently up-regulation of Dsg3 however has been reported in squamous cell carcinoma (SCC) of head and neck although the role of Dsg3 in cancer remains unknown. This study aimed to address this question with a focus on cell migration and invasion in various oral SCC cell lines and SqCC/Y1 cells in which both knockdown and over expression of Dsg3 has been achieved.

Methods: We performed the study using several three-dimensional culture settings including transwell migration/invasion assays and organotypic raft culture, the latter of which is more representative of the peritumoural tissue than transwell migration/invasion assays.

Results: We showed that SCC4 cell line, which have lost majority of desmosomal genes and proteins, exhibited a significantly enhanced cell migration. In contrast, when we performed the same assays in SqCC/Y1 cell lines with over expression or down regulation of Dsg3, we found that cells with over expression of Dsg3 exhibited a significantly augmented cell migration and invasion. This finding was further confirmed by the organotypic raft culture that showed a significantly increased cell invasion index in these cell lines compared with the vector control and knockdown cells. By contrast, cells with Dsg3 knockdown did not show any enhancement of cell migration and invasion.

Conclusion: Taken together, our findings suggest that although desmosomes have an overall suppression role in cell migration, Dsg3 plays a role in cancer by promoting cell migration and invasion, the notion proposed by others in the literature.