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

abstract

  • 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.

authors

  • Pangon, L
  • Ng, Irvin
  • Giry-Laterriere, M
  • Currey, N
  • Morgan, A
  • Benthani, F
  • Tran, PN
  • Al-Sohaily, S
  • Segelov, E
  • Parker, BL
  • Cowley, MJ
  • Wright, DC
  • St Heaps, L
  • Carey, L
  • Rooman, I
  • Kohonen-Corish, MRJ

publication date

  • 2016

has subject area