Interplay of ELF5, GATA-3 and FLI-1 Regulate Malignant Transformation of Keratinocytes

Using CRISPR-Cas9 knockout technology, functional studies along with transcript and protein analysis, loss of ELF5 in immortalised healthy keratinocytes (HaCaT) leads to decreased ability of cells to differentiation and increased migration, invasion and tumourigenicity, in vitro. While overexpression of ELF5 leads to inhibition of cell migration and proliferation in keratinocytes and in skin cancer cell lines (A431 and SCC-9), in vitro.

Further analysis using RNA transcriptomics has uncovered that GATA-3 and FLI-1 are key molecular targets of ELF5 in keratinocytes. ELF5 regulation of both GATA-3 and FLI-1 is required to maintain the balance between healthy keratinocytes (proliferation/differentiation) and to prevent precancerous cell formation (tumourigenicity). Our data indicates that ELF5 plays pivotal role in preventing malignant transformation of keratinocytes and potentially suppresses skin tumourigenesis, which could be targeted for future drug treatments for cSCC.

Better understanding of the underlying mechanisms by which ELF5 regulates gene expression and consequently cell activity will provide new knowledge that can be translated into long-term benefits for patients with precancerous legions to cSCC.