TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000241261
  • Gene Name:TRAIL
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:JNK-p53
  • 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 cell lines HCT116

Other information

  • Title:Urokinase-type plasminogen activator receptor regulates apoptotic sensitivity of colon cancer HCT116 cell line to TRAIL via JNK-p53 pathway.
  • Journal:Apoptosis : an international journal on programmed cell death
  • Published:2014
  • PubMed ID:25113506
  • Abstract:The urokinase-type plasminogen activator receptor (uPAR) serves not only as an anchor for urokinase-type plasminogen activator but also participates in intracellular signal transduction events. In this study, we investigated whether uPAR could modulate TRAIL-induced apoptosis in human colon cancer cells HCT116. Using an antisense strategy, we established a stable HCT116 cell line with down-regulated uPAR. The sensitivity to TRAIL-induced apoptosis was evaluated by FACS analysis. Our results show that the inhibition of uPAR could sensitize HCT116 to TRAIL-induced apoptosis. uPAR inhibition changed the expression of mitochondrial apoptotic pathway proteins, including Bcl-2, Bax, Bid and p53, in a pro-apoptotic manner. We also found that the inhibition of uPAR down-regulated the phosphorylation of FAK, ERK and JNK. The inhibition of p53 by RNA interference rescued cells from enhanced apoptosis, thus indicating that p53 is critical for enhancing TRAIL-induced apoptosis. Furthermore, JNK, but not ERK, inhibition involved in the up-regulation of p53. JNK negatively regulated p53 protein level. Overall, our results show that uPAR inhibition can sensitize colon cancer cells HCT116 to TRAIL-induced apoptosis via active p53 and mitochondrial apoptotic pathways that JNK inhibition is involved.
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