JRK is a positive regulator of β-catenin transcriptional activity commonly overexpressed in colon, breast and ovarian cancer

L Pangon, I Ng, M Giry-Laterriere, N Currey, A Morgan, F Benthani, P N Tran, S Al-Sohaily, E Segelov, B L Parker, M J Cowley, D C Wright, L St Heaps, L Carey, I Rooman, M R J Kohonen-Corish

Onderzoeksoutput: Articlepeer review

15 Citaten (Scopus)

Samenvatting

The loss of β-catenin inhibitory components is a well-established mechanism of carcinogenesis but β-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 β-catenin pathway. We proceeded to validate the oncogenic role of JRK in colon cancer cells and primary tumors. Consistent with a β-catenin activator function, depletion of JRK in several cancer cell lines repressed β-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 β-catenin target genes and increased cell proliferation. This study shows that JRK is required for β-catenin hyperactivity regardless of the adenomatous polyposis coli/β-catenin mutation status and targeting JRK presents new opportunities for therapeutic intervention in cancer.

Originele taal-2English
Pagina's (van-tot)2834-2841
Aantal pagina's8
TijdschriftONCOGENE
Volume35
Nummer van het tijdschrift22
DOI's
StatusPublished - 2 jun 2016

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