TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000674920
  • Gene Name:ATF4
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

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

Disease basic infommation

  • Disease:hepatocellular carcinoma
  • Tissue:HEK-293T, SNU398, HT1080 cells

Other information

  • Title:YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis.
  • Journal:EMBO molecular medicine
  • Published:2021
  • PubMed ID:34664408
  • Abstract:Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In this study, a combination of shRNA-mediated synthetic lethality screening and transcriptomic analysis revealed the transcription factors YAP/TAZ as key drivers of Sorafenib resistance in hepatocellular carcinoma (HCC) by repressing Sorafenib-induced ferroptosis. Mechanistically, in a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling HCC cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. Our study uncovers a critical role of YAP/TAZ in the repression of ferroptosis and thus in the establishment of Sorafenib resistance in HCC, highlighting YAP/TAZ-based rewiring strategies as potential approaches to overcome HCC therapy resistance.
@Copyright Harbin Medical University
　The 2nd Affiliated Hospital of Harbin Medical University
　 备案号：鲁ICP备2022025566号-3