JRK is a positive regulator of ß-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer.
Oncogene
; 35(22): 2834-41, 2016 06 02.
Article
em En
| MEDLINE
| ID: mdl-26455321
ABSTRACT
The loss of ß-catenin inhibitory components is a well-established mechanism of carcinogenesis but ß-catenin hyperactivity can also be enhanced through its coactivators. Here we first interrogated a highly validated genomic screen and the largest repository of cancer genomics data and identified JRK as a potential new oncogene and therapeutic target of the ß-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a ß-catenin activator function, depletion of JRK in several cancer cell lines repressed ß-catenin transcriptional activity and reduced cell proliferation. Importantly, JRK expression was aberrantly elevated in 21% of colorectal cancers, 15% of breast and ovarian cancers and was associated with increased expression of ß-catenin target genes and increased cell proliferation. This study shows that JRK is required for ß-catenin hyperactivity regardless of the adenomatous polyposis coli/ß-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Transcrição Gênica
/
Neoplasias da Mama
/
Proteínas Nucleares
/
Regulação Neoplásica da Expressão Gênica
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Neoplasias do Colo
/
Beta Catenina
Limite:
Female
/
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Austrália