USP20 positively regulates tumorigenesis and chemoresistance through ß-catenin stabilization.
Cell Death Differ
; 25(10): 1855-1869, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-29867130
ABSTRACT
ß-catenin is a major transcriptional activator of the canonical Wnt/ß-catenin signaling pathway. It is important for a series of biological processes including tissue homeostasis, and embryonic development and is involved in various human diseases. Elevated oncogenic activity of ß-catenin is frequently observed in cancers, which contributes to survival, metastasis and chemo-resistance of cancer cells. However, the mechanism of ß-catenin overexpression in cancers is not well defined. Here we demonstrate that the deubiquitination enzyme USP20 is a new regulator of the Wnt/ß-catenin signaling pathway. Mechanistically, USP20 regulates the deubiquitination of ß-catenin to control its stability, thereby inducing proliferation, invasion and migration of cancer cells. High expression of USP20 correlates with increased ß-catenin protein level in multiple cancer cell lines and patient samples. Moreover, knockdown of USP20 increases ß-catenin polyubiquitination, which enhances ß-catenin turnover and cell sensitivity to chemotherapy. Collectively, our results establish the USP20-ß-catenin axis as a critical regulatory mechanism of canonical Wnt/ß-catenin signaling pathway with an important role in tumorigenesis and chemo response in human cancers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistencia a Medicamentos Antineoplásicos
/
Ubiquitina Tiolesterase
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Beta Catenina
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2018
Tipo de documento:
Article