Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway.
Science
; 364(6441)2019 05 17.
Article
em En
| MEDLINE
| ID: mdl-31097636
ABSTRACT
Activation of tumor suppressors for the treatment of human cancer has been a long sought, yet elusive, strategy. PTEN is a critical tumor suppressive phosphatase that is active in its dimer configuration at the plasma membrane. Polyubiquitination by the ubiquitin E3 ligase WWP1 (WW domain-containing ubiquitin E3 ligase 1) suppressed the dimerization, membrane recruitment, and function of PTEN. Either genetic ablation or pharmacological inhibition of WWP1 triggered PTEN reactivation and unleashed tumor suppressive activity. WWP1 appears to be a direct MYC (MYC proto-oncogene) target gene and was critical for MYC-driven tumorigenesis. We identified indole-3-carbinol, a compound found in cruciferous vegetables, as a natural and potent WWP1 inhibitor. Thus, our findings unravel a potential therapeutic strategy for cancer prevention and treatment through PTEN reactivation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-myc
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Anticarcinógenos
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Proteínas Supressoras de Tumor
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Ubiquitina-Proteína Ligases
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PTEN Fosfo-Hidrolase
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Indóis
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
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Male
Idioma:
En
Revista:
Science
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos