These data identify a new transcriptional programme mediated by p63 regulation of the Basonuclin 1 transcription factor in squamous cell carcinomas and provide a novel link of p63 with the regulation of ribosomal biogenesis in epithelial cancer.
Remarkably, a similar spectrum of phenotypic alterations is observed in human syndromes resulting from Tp63 gene mutations. p63 is an important hub in the transcriptional and signaling networks of epithelial cells; thus, it is not surprising that dysregulation of this transcription factor is associated with squamous cell carcinoma.
The major protein isoform of p63 expressed in SCC is ΔNp63α, an N-terminally truncated form which functions as a key SCC cell survival factor by mechanisms that are unclear.
This study indicates that p63 is a target gene of the proposed keratinocyte-specific TGF-β signal pathway for suppression of the malignant conversion of SCC.
Furthermore, SOX2 overexpression can induce the expression of the squamous markers p63 and keratin 6, supporting the idea that SOX2 might be implicated in SCC differentiation.
A common set of genes dysregulated in lung cancer was obtained, including BPA1, DUSP6, ASCL1, RNAS1 and S100P. p63 and CK 5/6 p63 are useful for differentiating adenocarcinoma and small cell lung cancer from squamous cell carcinoma.
We have previously reported that down-regulation of p63 was accompanied with epithelial-to-mesenchymal transition (EMT) by Snail-expressing SCC cells, in which re-expression of DeltaNp63alpha diminished their invasiveness (Higashikawa K, Yoneda S, Tobiume K, Taki M, Shigeishi H, Kamata N. Snail-induced down-regulation of DeltaNp63alpha acquires invasive phenotype of human squamous cell carcinoma.Cancer Res 2007;67:9207-13).
We found that Snail-induced epithelial-to-mesenchymal transition (EMT) is accompanied by down-regulation of p63 in human squamous cell carcinomas (SCC).
The p53 family member p63 plays an essential role in the developing epithelium, and overexpression of the DeltaNp63alpha isoform is frequently observed in human squamous cell carcinomas (SCCs).
To gain further information on the role of p63 expression in human tumours, we used quantitative real-time RT-PCR to study individual p63 isoforms in squamous cell carcinomas of the head and neck (SCCHN).
We investigated the expression of the two N-terminal p63 isoforms (TA and deltaN isoforms) in human primary well-differentiated buccal squamous cell carcinoma.
Expression of deltaNp63 was identical to expression of pan-p63 in the vast majority of samples. p63 gene amplification was found in 2 of 10 (20.0%) investigated SCCs and in 1 of 10 (10.0%) ADCs.