Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
FEBS Lett. 2011 Jul 21;585(14):2144-50. doi: 10.1016/j.febslet.2011.05.034. Epub 2011 May 27.
One major obstacle in the clinical application of TRAIL as a cancer therapeutic agent is the acquisition of TRAIL resistance. We found that deficiency of TRADD sensitizes cells to TRAIL-induced apoptosis. Enhanced cell death in TRADD(-/-) MEFs is associated with defective NF-κB activation, indicating that the pro-survival function of TRADD in TRAIL signaling is mediated at least in part via NF-κB activation. Moreover, siRNA knock-down of TRADD in cancer cells sensitizes them to TRAIL-induced apoptosis. Thus, TRADD has a survival role in TRAIL signaling and may be one potential target for overcoming TRAIL resistance in cancer therapy.
TRAIL 在癌症治疗中的临床应用主要存在一个障碍，就是获得 TRAIL 耐药性。我们发现，TRADD 的缺乏会使细胞对 TRAIL 诱导的凋亡敏感。TRADD(-/-) MEFs 中增强的细胞死亡与 NF-κB 激活缺陷有关，表明 TRADD 在 TRAIL 信号中的生存功能至少部分是通过 NF-κB 激活介导的。此外，在癌细胞中用 siRNA 敲低 TRADD 会使它们对 TRAIL 诱导的凋亡敏感。因此，TRADD 在 TRAIL 信号中具有生存作用，可能是克服癌症治疗中 TRAIL 耐药性的一个潜在靶点。
