Squamous cell carcinomas (SCCs) of the skin and head and neck region remain some of the world’s most common cancers. Snail2 is a zinc finger transcription factor that is commonly upregulated in HNSCCs and is associated with tumour recurrence and metastasis. In mouse models, Snail2 has been shown to be required for epidermal migration in healing wounds. We have previously shown that Snail2 is capable of inhibiting terminal differentiation, a hallmark that is often associated with tumorigenesis and keratinocyte migration. Therefore, we aim to identify the mechanisms with which Snail2 can achieve this.
Snail2 was stably over-expressed in HN13, a non-tumorigenic oral keratinocyte cell line, and was shown to down-regulate ELF3 and Matriptase-1, genes both involved in terminal differentiation. Luciferase reporter assays demonstrated that Snail2 was indeed acting on the promoter of these genes to inhibit their expression. Furthermore, long-term culture experiments showed that Snail2 significantly inhibited desquamation. However, when either Matriptase-1 or ELF3 was re-expressed, desquamation was partially restored.
In vivo UV carcinogenesis studies have demonstrated that mice deficient in Matriptase-1 develop cutaneous SCCs at a faster rate than wildtype animals, indicating that Matriptase-1 plays a tumour suppressor role in the skin.