TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000394825
  • Gene Name:NR4A1
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:AXIN2/RNF12/ARKADIA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

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

Disease basic infommation

  • Disease:breast cancer
  • Tissue:Human cervical cancer HeLa cell line, human prostate cancer PC3 cell line, breast cancerNamru Mouse Mammary Gland NMuMG cell line, human MDA-MB-231 cell line and human MCF10A-RAStransformed cell line, human HaCAT keratinocyte cell line, human HN5 cell line and primary MEFs

Other information

  • Title:Nuclear receptor NR4A1 promotes breast cancerinvasion and metastasis by activating TGF-β signalling.
  • Journal:Nat Commun
  • Published:2014
  • PubMed ID:24584437
  • Abstract:In advanced cancers, the TGF-β pathway acts as an oncogenic factor and is considered to be a therapeutic target. Here using a genome-wide cDNA screen, we identify nuclear receptor NR4A1 as a strong activator of TGF-β signalling. NR4A1 promotes TGF-β/SMAD signalling by facilitating AXIN2-RNF12/ARKADIA-induced SMAD7 degradation. NR4A1 interacts with SMAD7 and AXIN2, and potently and directly induces AXIN2 expression. Whereas loss of NR4A1 inhibits TGF-β-induced epithelial-to-mesenchymal transition and metastasis, slight NR4A1 ectopic expression stimulates metastasis in a TGF-β-dependent manner. Importantly, inflammatory cytokines potently induce NR4A1 expression, and potentiate TGF-β-mediated breast cancer cell migration, invasion and metastasis in vitro and in vivo. Notably, NR4A1 expression is elevated in breast cancer patients with high immune infiltration and its expression weakly correlates with phosphorylated SMAD2 levels, and is an indicator of poor prognosis. Our results uncover inflammation-induced NR4A1 as an important determinant for hyperactivation of pro-oncogenic TGF-β signalling in breast cancer.
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