The role of P63 in cancer, stem cells and cancer stem cells

Abstract

The transcription factor p63 has important functions in tumorigenesis, epidermal differentiation and stem cell self-renewal. The TP63 gene encodes multiple protein isoforms that have different or even antagonistic roles in these processes. The balance of p63 isoforms, together with the presence or absence of the other p53 family members, p73 and p53, has a striking biological impact. There is increasing evidence that interactions between p53-family members, whether cooperative or antagonistic, are involved in various cell processes. This review summarizes the current understanding of the role of p63 in tumorigenesis, metastasis, cell migration and senescence. In particular, recent data indicate important roles in adult stem cell and cancer stem cell regulation and in the response of cancer cells to therapy.

Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas

“…[35][36][37] Finally, a role for ⌬Np63 in the regulation of stem cell dynamics recently has been proposed. 38,39 TP63 rearrangements were found exclusively in 3 PTCL subtypes: PTCL, NOS; ALK-negative ALCL; and primary cutaneous ALCL. Of 5 PTCLs, NOS with TP63 rearrangements, 4 (80%) had CD30 staining in Ն 80% of cells (the threshold used by the International Peripheral T-cell Lymphoma Project, which found 5-year overall survival rates of only 19% in CD30-positive PTCLs, NOS.…”

p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53

“…In addition to the full length a isoform, two isoforms have been described: a b isoform (skipping exon 13) and a g isoform (alternative exon 15, following exon 10, with its stop codon and distinct 3 0 -UTR. In silico analysis predicted the d isoform (skipping exon [12][13] and the e isoform (premature termination in intron 10 retaining the 5 0 -portion of intron 10 with a stop codon p63 is the most recently discovered but the most ancient member of the p53 family [8][9][10][11][12][13][14][15]28 ( Figure 1). As indicated above, p63 is transcribed from two promoters, giving rise to proteins that may (TAp63 isoforms) or may not (DNp63 isoforms) contain the TA, 1 and alternative splicing at the 3 0 -end produces additional proteins (a-e isoforms), 29 although there is no in vivo evidence for two latter isoforms.…”

ΔNp63α represses anti-proliferative genes via H2A.Z deposition

“…SCCs frequently accrue both loss-of-function mutations of the tumor suppressor p53 and overexpression of the oncogene DNp63a, suggesting that these two oncogenic events are not functionally redundant (Nekulova et al 2011). In order to investigate the possible functional interplay between DNp63a and p53, we screened a panel of SCC cell lines in search of those expressing wild-type versions of both genes.…”