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1.
J Transl Med ; 13: 248, 2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-26219351

RESUMO

BACKGROUND: A previous report has shown that LGALS3BP (also known as 90K or Mac-2 BP) has antitumor activity in colorectal cancer (CRC) via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of ß-catenin. The role of LGALS3BP in CRC prognosis was investigated. METHODS: The role of LGALS3BP on CRC progression and clinical prognosis was analyzed by combining cell cultures, in vitro assays, and immunohistochemistry. RESULTS: Silencing of LGALS3BP in HCT-116 human colon cancer cells resulted in enhanced ß-catenin expression that was reversed by addition of human recombinant LGALS3BP. Moreover, intra-tumor delivery of LGALS3BP reduced tumor growth of xenografts originating from LGALS3BP-silenced HCT-116 cells. Finally, in a series of 196 CRC patients, LGALS3BP expression in tumor tissue associated with clinical outcome. Patients with high LGALS3BP expression had lower risk of relapse and a longer overall survival time than those with low LGALS3BP expression. Multivariate analyses confirmed LGALS3BP expression status as the only independent prognostic factor of survival. CONCLUSIONS: These results provide evidence that low expression of LGALS3BP participates in malignant progression of CRC and implicates poor prognosis, highlighting its augmentation as a potential therapeutic approach.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Glicoproteínas/metabolismo , Animais , Proliferação de Células , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Inativação Gênica , Células HCT116 , Células HEK293 , Humanos , Imuno-Histoquímica , Injeções Intralesionais , Estimativa de Kaplan-Meier , Camundongos Nus , Análise Multivariada , Prognóstico , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
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