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Expression of Epsin3 and its interaction with Notch signalling in oral epithelial dysplasia and oral squamous cell carcinoma

Lookup NU author(s): Dr Halah Ahmed, Sadat Aziz, Professor Marco Carrozzo, Professor Ruth Valentine

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2023 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.Background: Most oral squamous cell carcinoma patients present with late-stage disease. Early detection of the disease is considered to be the most effective way of improving patient outcomes. Several biomarkers have been identified as indicators of oral cancer development and progression; however, none have been translated into clinical practice. In this study, we have investigated the role of Epsin3, an endocytic adaptor protein, and Notch1, a transmembrane signalling protein, in oral carcinogenesis with a view to explore their potential as biomarkers. Methods: Oral cancer cell lines and a normal oral keratinocyte cell line were used together with tissue samples of normal oral mucosa (n = 21), oral epithelial dysplasia (n = 74) and early stage (Stages I and II) oral squamous cell carcinoma (n = 31). Immunocytochemical staining, immunoblotting and real-time quantitative polymerase chain reaction (PCR) were performed to assess protein as well as gene expression levels. Results: The expression levels of Epsin3 and Notch1 mRNA and protein are variable across different oral squamous cell carcinoma derived cell lines. Epsin3 was upregulated in oral epithelial dysplasia and oral squamous cell carcinoma tissues compared with normal epithelium. Overexpression of Epsin3 resulted in a significant reduction of Notch1 expression in oral squamous cell carcinoma. Notch1 was generally downregulated in the dysplasia and oral squamous cell carcinoma samples. Conclusion: Epsin3 is upregulated in oral epithelial dysplasia and oral squamous cell carcinoma and has the potential to be used as a biomarker for oral epithelial dysplasia. Notch signalling is downregulated in oral squamous cell carcinoma, possibly through an Epsin3-induced de-activation pathway.


Publication metadata

Author(s): Ahmed H, Paterson I, Aziz SA, Cremona O, Robinson M, Carrozzo M, Valentine RA

Publication type: Article

Publication status: Published

Journal: Journal of Oral Pathology and Medicine

Year: 2023

Volume: 52

Issue: 8

Pages: 710-717

Print publication date: 01/09/2023

Online publication date: 20/06/2023

Acceptance date: 26/05/2023

Date deposited: 12/07/2023

ISSN (print): 0904-2512

ISSN (electronic): 1600-0714

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1111/jop.13460

DOI: 10.1111/jop.13460


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