Tools
Tools
Patel, HJ, 2025. Investigation into the role of ELF5 during the initiation and development of cutaneous squamous cell carcinoma. PhD, Nottingham Trent University.
Preview |
Text
Hetal Patel 2026.pdf - Published version Download (5MB) | Preview |
Abstract
Cutaneous squamous cell carcinoma (cSCC), the second most prevalent epithelial cancer, originates from epidermal keratinocytes. ELF5 (E74-like factor 5) a transcription factor from epithelium specific Members of the ETS transcription factor subfamily are critical for maintaining epithelial development, tissue homeostasis, and preventing epithelial-derived cancers. Malignant transformation of keratinocytes involves the disruption of the progenitor differentiation program causing keratinocytes to fail to complete the differentiation process, leading to dysplastic epithelium and precancerous cells in skin. However, the precise mechanisms that causes the failure of keratinocytes to differentiate completely is not well understood. This study highlights a novel tumour-suppressive function of ELF5 in keratinocytes. We observed high levels of ELF5 expression in normal human skin, particularly within both basal and suprabasal layers, whereas its expression was notably diminished in cSCC biopsy samples. Using CRISPR-Cas9-mediated gene knockout, alongside transcriptomic and proteomic analyses, we demonstrated that loss of ELF5 in non-tumorigenic keratinocytes (HaCaT cells) compromises their ability to differentiate and enhances their migratory, invasive, and tumorigenic potential 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 findings suggest that ELF5 serves a critical role in safeguarding keratinocytes against malignant transformation and may act as a suppressor of skin tumour development. Uncovering the molecular pathways regulated by ELF5 will offer important insights, with potential applications in developing future therapeutic strategies for cSCC and in improving outcomes for individuals with precancerous skin lesions.
| Item Type: | Thesis |
|---|---|
| Creators: | Patel, H.J. |
| Contributors: | Name Role NTU ID ORCID |
| Date: | June 2025 |
| Rights: | This work is the intellectual property of the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully references, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed in the owner(s) of the Intellectual Property Rights. |
| Divisions: | Schools > School of Science and Technology |
| Record created by: | Laura Borcherds |
| Date Added: | 09 Apr 2026 11:56 |
| Last Modified: | 09 Apr 2026 11:56 |
| URI: | https://irep.ntu.ac.uk/id/eprint/55523 |
https://orcid.org/0000-0002-9051-7681Actions (login required)
 |
Edit View |
Statistics
Views
Views per month over past year
Downloads
Downloads per month over past year
