N-myc downstream-regulated gene 1 promotes apoptosis in colorectal cancer via up-regulating death receptor 4.
N-myc downstream-regulated gene 1 promotes apoptosis in colorectal cancer via up-regulating death receptor 4.
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N-myc下游调节基因1通过上调死亡受体4促进结直肠癌细胞凋亡
DOI：
10.18632/oncotarget.19658
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发表时间：
2017-10-10
期刊：
影响因子：
--
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Zhang X;Feng B;Zhu F;Yu C;Lu J;Pan M;He Z;Wangpu X;Sun J;Yang X
本研究的目的是评估N-myc下游调节基因1（NDRG1）在结直肠癌（CRC）患者中的临床意义，并探讨NDRG1在CRC细胞凋亡中的作用机制。在目前的研究中，我们发现NDRG1是CRC患者的预后标志物。此外，NDRG1 表达与肿瘤大小和临床 TNM 分期呈负相关，表明 NDRG1 可能通过抑制 CRC 增殖或诱导细胞凋亡来充当肿瘤抑制因子。一致地，在 NDRG1 存在的情况下，在体外和体内观察到大量细胞凋亡。从机制的角度来看，我们发现 NDRG1 能够防止死亡受体 4 被 MARCH-8 诱导的降解，MARCH-8 是膜相关 RING-CH (MARCH) 泛素连接酶家族的成员。因此，表达 NDRG1 的 CRC 细胞对针对死亡受体的试剂更加敏感，例如肿瘤坏死因子相关的凋亡诱导配体 (TRAIL)。此外，NDRG1的促凋亡作用也在小鼠异种移植模型中得到了验证。总之，我们的结果进一步揭示了 NDRG1 在死亡受体引发的细胞凋亡中的关键作用，并证明了一种新的标记物可以在未来的临床研究中预测 CRC 对 TRAIL 治疗的敏感性。
The aim of this study was to evaluate the clinical significance of N-myc downstream-regulated gene 1 (NDRG1) in colorectal cancer (CRC) patients and to explore the mechanisms governing the role of NDRG1 in apoptosis of CRC cells. In the current study, we found that NDRG1 was a prognostic marker of CRC patients. Moreover, NDRG1 expression negatively correlated to tumor size and clinical TNM stage, suggesting that NDRG1 might act as a tumor suppressor by inhibiting proliferation or inducing apoptosis in CRC. Consistently, substantial apoptosis was observed in vitro and in vivo in the presence of NDRG1. From a mechanistic standpoint, we discovered that NDRG1 was able to prevent death receptor 4 from degradation induced by MARCH-8, a member of the membrane-associated RING-CH (MARCH) ubiquitin ligase family. As a consequence, CRC cells expressing NDRG1 were more sensitive to reagents targeting death receptors such as tumor necrosis factor-related apoptosis-inducing ligands (TRAIL). Additionally, the pro-apoptotic effect of NDRG1 was also validated in mouse xenograft model. In conclusion, our results provided further insights of the pivotal role of NDRG1 in apoptosis initiated by death receptors and demonstrated a novel marker to predict the sensitivity of CRC to TRAIL treatment in future clinical study.
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DOI：
10.1073/pnas.1503683112
发表时间：
2015-09-15
影响因子：
11.1
作者：
Croessmann, Sarah;Wong, Hong Yuen;Park, Ben Ho
通讯作者：
Park, Ben Ho
影响因子：
4.8
作者：
Guo, Y;Srinivasula, SM;Alnemri, ES
通讯作者：
Alnemri, ES
影响因子：
56.9
作者：
LOWE, J;STOCK, D;HUBER, R
通讯作者：
HUBER, R
影响因子：
4.6
作者：
Luo EC;Chang YC;Sher YP;Huang WY;Chuang LL;Chiu YC;Tsai MH;Chuang EY;Lai LC
通讯作者：
Lai LC
DOI：
10.1158/1078-0432.ccr-10-2874
发表时间：
2011-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kang Z;Chen JJ;Yu Y;Li B;Sun SY;Zhang B;Cao L
通讯作者：
Cao L