TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000374994
  • Gene Name:TGFBR1
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:TGF-β
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

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

Disease basic infommation

  • Disease:lung cancer
  • Tissue:A549

Other information

  • Title:BIX02189 inhibits TGF-β1-induced lung cancer cell metastasis by directly targeting TGF-β type I receptor
  • Journal:Cancer Lett
  • Published:2016
  • PubMed ID:27543359
  • Abstract:Transforming growth factor-β1 (TGF-β1) promotes tumor metastasis by inducing an epithelial-to-mesenchymal transition (EMT) in cancer cells. In this study, we investigated the effects of BIX02189 and XMD8-92, pharmacologic inhibitors of the MEK5 [mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK)5] signaling pathway, on the EMT and migration of cancer cells induced by TGF-β1. In human A549 lung cancer cells, TGF-β1-induced EMT, cell motility, and expression of matrix metalloproteinase-2 were completely inhibited by BIX02189, but not by XMD8-92 or small interference RNAs specific to MEK5 and ERK5. Interestingly, BIX02189 strongly blocked the activation of TGF-β1 signaling components, and this inhibitory effect was not reproduced by MEK5 inhibition. Molecular docking simulation and kinase assays revealed that BIX02189 binds directly to the ATP-binding site of the TGF-β receptor type I (TβRI) and suppresses its kinase activity. Finally, the anti-metastatic effect of BIX02189 was validated in a TβRI-derived A549 xenograft mouse model. Collectively, these findings newly characterize BIX02189 as a potent inhibitor of TβRI that can block the tumor metastatic activity of TGF-β1.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3