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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.

Abbreviations

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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Correspondence to Borivoj Vojtesek.

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Nekulova, M., Holcakova, J., Coates, P. et al. The role of P63 in cancer, stem cells and cancer stem cells. Cell Mol Biol Lett 16, 296–327 (2011). https://doi.org/10.2478/s11658-011-0009-9

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  • DOI: https://doi.org/10.2478/s11658-011-0009-9

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