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. 2011 Mar 20;16(2):296–327. doi: 10.2478/s11658-011-0009-9

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

Marta Nekulova 1, Jitka Holcakova 1, Philip Coates 2, Borivoj Vojtesek 1,✉
PMCID: PMC6275999  PMID: 21442444

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.

Key words: p63, TAp63, ΔNp63, p53 family, Cancer, Stem cells

Full Text

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Abbreviations used

APAF-1

apoptotic protease activating factor 1

ATM

ataxia telangiectasia mutated

BAD

BCL-2 associated agonist of cell death

BAX

BCL2-associated X protein

BRCA2

breast cancer 2, early onset

c-Abl

Abelson murine leukemia oncogene

Cables1

CDK and ABL1 enzyme substrate 1

CASP10

caspase 10

CDHs

cadherins

CLDN1

claudin 1

CSCs

cancer stem cells

DBD

DNA-binding domain

EGR3

early growth response 3

FRAS1

Fraser syndrome 1

HNSCC

squamous cell carcinoma of the head and neck

HOXC4

homeobox C4

ICAM

inter-cellular adhesion molecule

IER3

immediate early response 3

IHH

Indian hedgehog

IKKα

inhibitor of nuclear factor kappa-B kinase subunit alpha

JAG1

jagged 1

MDM2

murine double minute 2

MEFs

mouse embryonic fibroblasts

MRE11

meiotic recombination 11 homolog

mTOR

mammalian target of rapamycin

Notch1

Notch homolog 1, translocation-associated

OD

oligomerization domain

PCNA

proliferating cell nuclear antigen

PERP

p53 apoptosis effector related to PMP-22

RBP

RNA-binding protein

REs

responsive elements

SAM

sterile alpha motif

SHH

sonic hedgehog

STAT3

signal transducer and activator of transcription 3

SUMO1

small ubiquitin-related modifier 1

TA

transactivation domain

TRAIL

TNF-related apoptosis-inducing ligand

Tprg

tumor protein p63 regulated

Wnt

wingless-type MMTV integration site family member

YAP

Yes-associated protein

ZEB1

zinc finger E-box binding homeobox 1

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