Mutant p53 oncogenic functions in cancer stem cells are regulated by WIP through YAP/TAZ.
Oncogene
; 36(25): 3515-3527, 2017 06 22.
Article
em En
| MEDLINE
| ID: mdl-28166194
ABSTRACT
Wild-type p53 (wtp53) is described as a tumour suppressor gene; mutations in this gene occur in many human cancers and promote oncogenic capacity. Here, we establish that the oncogenic activity of mutant p53 (mtp53) is driven by the WASP-interacting protein (WIP). WIP knockdown from mtp53-expressing glioblastoma and breast cancer cells (BCC) greatly reduced proliferation and growth capacity of cancer stem cell (CSC)-like cells and decreased CSC-like markers (CD133, CD44 or YAP/TAZ). mtp53 overexpression in human astrocytes enhanced their proliferative capacity in suspension culture and increased expression of CSC markers and WIP. WIP knockdown compromised tumour glioblastoma and BCC growth capacity in vivo. We show that WIP is phosphorylated by AKT2 and is regulated by mtp53/p63 through enhancement of PI3K/AKT2-mediated integrin/receptor recycling pathways. WIP regulates this oncogenic pathway by controlling YAP/TAZ stability. We thus establish a new CSC signalling pathway downstream of mtp53 in which AKT2 regulates WIP and controls YAP/TAZ stability.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Fatores de Transcrição
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Células-Tronco Neoplásicas
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Neoplasias da Mama
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Transdução de Sinais
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Proteína Supressora de Tumor p53
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Glioblastoma
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Proteínas do Citoesqueleto
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas Adaptadoras de Transdução de Sinal
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Espanha