P40 Characterization of ELF5 and its role in the initiation and development of cutaneous squamous cell carcinomas

Abstract Introduction and aims The human skin is a highly complex organ that functions as a primary protective barrier against environmental adversities while maintaining physiological homeostasis. Cutaneous squamous cell carcinoma (cSCC) originates from epidermal keratinocytes and ranks as the second most prevalent epithelial malignancy. Elf5 is classified as a member of the epithelium-specific Ets subfamily of transcription factors, which is critical for epithelial differentiation, maintenance of homeostasis, and the inhibition of tumorigenesis. Nonetheless, the precise role of Elf5 in the modulation of cSCC initiation and progression remains to be elucidated. Our investigation provides novel insights into the emergent function of ELF5 as a tumour suppressor within the cutaneous milieu. Methods We employed CRISPR knockdown methodology in conjunction with transcriptomic and proteomic analyses. Results We discovered that the ablation of ELF5 results in a diminished capacity of healthy keratinocytes to undergo differentiation, coupled with enhanced migratory and proliferative tendencies in both nonmalignant and malignant cells, in vitro. Conversely, the overexpression of ELF5 is associated with a suppression of cellular migration and proliferation within cancer cell lines in vitro, thereby indicating that ELF5 assumes a critical role as a tumour suppressor in the skin. Subsequent investigations utilizing RNA transcriptomic analyses will clarify the molecular targets of the differentially expressed and coregulated genes observed between healthy keratinocytes and their malignant counterparts. Conclusions Our findings suggest that ELF5 is instrumental in thwarting the malignant transformation of keratinocytes and in inhibiting skin tumorigenesis, thus representing a potential target for future therapeutic interventions in cSCC. A comprehensive understanding of the mechanisms through which ELF5 regulates gene expression and, consequently, cellular behaviour will yield new insights that can be translated into enduring benefits for patients suffering from precancerous lesions progressing to cSCC.