Abstract
P63, and in particular the most expressed ΔNp63α isoform, seems to have a critical role in the outcome of head and neck cancer. Many studies have been conducted to assess the possible use of p63 as a prognostic marker in squamous cell carcinoma cancers, but the results are still not well-defined. Moreover, a clear relationship between the expression of ΔNp63α and the presence of high-risk HPV E6 and E7 oncoproteins has been delineated. Here we describe how ΔNp63α is mostly expressed in HPV-positive compared to HPV-negative head and neck cancer cell lines, with a very good correlation between ΔNp63α mRNA and protein levels.
Highlights
The p53 family of transcription factors, including p53 (TP53), p63 (TP63), and p73 (TP73), are key players in tumor development and formation (Vousden and Prives, 2009)
In this study we confirmed that HPV16 E6/E7 expression is able to regulate Np63α transcriptionally, increasing both its mRNA and protein levels in transduced human epidermal keratinocytes (HKs)
The link between human papillomavirus (HPV) oncoproteins and Np63α expression was confirmed in Head and Neck Cancers (HNC) HPV-positive cell lines where the lack of E6/E7 consistently decreased Np63α protein levels
Summary
The p53 family of transcription factors, including p53 (TP53), p63 (TP63), and p73 (TP73), are key players in tumor development and formation (Vousden and Prives, 2009). P63 and p73 are expressed from two distinct promoters, which produce two isoforms either containing or lacking the N-terminal transactivation domain (TAp63/p73 and DNp63/p73, respectively) (Deyoung and Ellisen, 2007). Np63α is the most abundant isoform detected in the basal layer of mucosa, skin, and other epithelial tissues and it is overexpressed in up to 80% of primary Head and Neck Cancers (HNC). Np63α expression is restricted to epithelial stem cells and the undifferentiated basal layer of stratified epithelia and is critical for the development and maintenance of stratified epithelial tissues (Oh et al, 2011). We have recently shown how Np63α is critical for cellular proliferation and migration in HNC cell lines (Citro et al, 2019)
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