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

L. Pangon, Irvin Ng, M. Giry-Laterriere, N. Currey, Ashleigh G 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

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10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2834-2841
Number of pages8
Issue number22
Publication statusPublished - 2 Jun 2016
Externally publishedYes

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