| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T77645 | ||||
| Target Name | Tumor necrosis factor receptor superfamily member 10A | ||||
| Target Type | Clinical Trial |
||||
| Action against Disease Model | RhApo2L/TRAIL | The combination of TRAIL treatment and cancer cell selective expression of TRAIL-death receptor DR4 induces cell death in TRAIL-resistant cancer cells. We generated a death receptor-4 (DR4)-expressing adenovirus (Ad-hTERT-DR4), in which the expression of DR4 is driven by the hTERT promoter. Upon infection, DR4 expression was slightly increased in cancer cell lines, and cell death was observed in TRAIL-resistant cancer cell lines but not in normal h uMan cells when DR4 infection was combined with TRAIL treatment. | [552584] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | In h uMan astrocytic t uMors, we detected DR4 promoter hypermethylation in 60% (n = 5) of diffuse astrocytomas WHO grade 2, in 75% (n = 8) of anaplastic astrocytomas WHO grade 3, and in 70% of glioblastomas WHO grade 4 (n = 33). DR4 is a cell surface protein restricted to glioma cells and is targeted by TRAIL. Glioma cell lines U373 and A172 harbored heavily methylated DR4 promoters, and 5-aza-2-deoxycytidine-mediated demethylation reconstituted DR4 expression in these cell lines. Functional knockdown of DR4 by DR4-specific small interfering RNA in TRAIL-sensitive gliomacell line LN18 significantly mitigated apoptosis induced by an agonistic anti-DR4 antibody. 5-Aza-2-deoxycytidine-mediated demethylation resulted in a functional reconstitution of DR4 on the cell surface of TRAIL-resistant glioma cell line U373 and sensitized U373 to TRAIL-mediated apoptosis. Suppression of DR4 by small interfering RNA in demethylated U373 successfully reestablished the TRAIL-resistant phenotype of U373. | [552584] | |||
| References | |||||
| Ref 552584 | The combination of TRAIL treatment and cancer cell selective expression of TRAIL-death receptor DR4 induces cell death in TRAIL-resistant cancer cells. Yonsei Med J. 2006 Feb 28;47(1):55-62. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.