TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000284240
  • Gene Name:THY1
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qPCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00398
  • Drug Name:Sorafenib
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:hepatocellular carcinoma
  • Tissue:cell line HuH1, HuH7, Hep3B, HLE, HLF, and SK-Hep-1

Other information

  • Title:Sorafenib suppresses extrahepatic metastasis de novo in hepatocellular carcinoma through inhibition of mesenchymal cancer stem cells characterized by the expression of CD90
  • Journal:Scientific Reports
  • Published:2017
  • PubMed ID:28900199
  • Abstract:Cancer stem cells (CSCs) are a pivotal target for eradicating hepatocellular carcinoma (HCC). We previously reported that distinctive CSCs regulating tumorigenicity (EpCAM+CSCs) and metastasis (CD90+CSCs) have different epithelial/mesenchymal gene expression signatures. Here, we examined the influence of sorafenib, a multiple-receptor tyrosine kinase inhibitor used as a first-line treatment for advanced HCC, on EpCAM+and CD90+CSCs. CD90+cells showed higher c-Kit gene/protein expression than EpCAM+cells. Sorafenib treatment reduced the number of CD90+cells with attenuated c-Kit phosphorylation, whereas it enriched the EpCAM+cell population. We evaluated the role of CD90+and EpCAM+CSCs in vivo by subcutaneously injecting these CSCs together in immune-deficient mice. We observed that sorafenib subtly affected the suppression of primary tumor growth maintained by EpCAM+CSCs, but completely inhibited the lung metastasis mediated by CD90+CSCs. We further evaluated the effect of sorafenib on extracellular vesicle (EV) production and found that sorafenib suppressed the production of EVs containing TGF-β mRNA in CD90+cells and inhibited the cell-cell communication and motility of EpCAM+cells. Our data suggest the following novel effects of sorafenib: suppressing CD90+CSCs and inhibiting the production of EVs regulating distant metastasis.