TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000649815
  • Gene Name:AKT
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:colon cancer
  • Tissue:Human colon cancer cells HT29, HT29-APC, HT29-b-gal, SW480, and HEK293

Other information

  • Title:Hypoxia triggers a Nur77-β-catenin feed-forward loop to promote the invasive growth of colon cancer cells.
  • Journal:Br J Cancer
  • Published:2014
  • PubMed ID:24423919
  • Abstract:Background:β-Catenin is a potent oncogenic protein in colorectal cancer (CRC), but the targets and regulation of this important signalling molecule are not completely understood. Hypoxia is a prominent feature of solid tumours that contributes to cancer progression. Methods:Here, we analysed the regulation between Nur77 and β-catenin under hypoxic conditions. Cell proliferation, migration, and invasion assays were performed to assess functional consequences. Results:We showed that hypoxia stimulated co-upregulation of β-catenin and Nur77 in a number of human CRC cell lines. Interestingly, expression of β-catenin and Nur77 by hypoxia formed a mutual feedback regulation circuits that conferred aggressive growth of CRC. Overexpression of β-catenin increased Nur77 transcription through hypoxia-inducible factor-1α rather than T-cell factor. Nur77-mediated activation of β-catenin by hypoxia was independent of both DNA binding and transactivation. Further, we showed that hypoxic activation of β-catenin was independent of the classical adenomatous polyposis coli and p53 pathways, but stimulated by phosphatidylinositol 3-kinase/Akt in a Nur77-dependent manner. Under hypoxic conditions, enhanced β-catenin and Nur77 expression synergistically stimulated CRC cell migration, invasion, and epithelial-mesenchymal transition. Conclusion:These findings provide a novel molecular mechanism for hypoxic CRCs that may contribute to tumour progression, and its targeting may represent an effective therapeutic avenue.
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