NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway.
NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway.
复制标题
NDRG1过表达通过调节Wnt信号通路促进食管鳞癌进展
DOI：
10.1080/15384047.2016.1210734
复制
发表时间：
2016-09
影响因子：
3.6
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Ai R;Sun Y;Guo Z;Wei W;Zhou L;Liu F;Hendricks DT;Xu Y;Zhao X
摘要N-myc下调基因1（NDRG 1）在多种恶性肿瘤中调节肿瘤生长和转移，在食管鳞状细胞癌（ESCC）中表达异常。在这里，我们发现NDRG 1在ESCC肿瘤组织中的过表达（91.9%，79/86）与食管癌患者的总体生存率低相关。当将NDRG 1异位过表达的慢病毒转导产生的KYSE 30 ESCC细胞系的稳定转染子中时，转导素样分裂增强子2（TLE 2）的表达急剧下降，但β-连环蛋白增加。从机制上讲，NDRG 1与TLE 2和β-catenin物理关联以影响Wnt通路。RNA干扰和TLE 2过表达研究表明，NDRG 1不能激活Wnt通路相比，同基因野生型对照。NDRG 1过表达通过激活Wnt信号通路诱导ESCC细胞发生上皮间质转化（EMT），降低E-cadherin的表达，增强Snail的表达。我们的研究阐明了NDRG 1通过影响TLE 2和β-catenin表达来调节食管癌细胞Wnt通路激活和EMT的机制。这表明NDRG 1在食管癌细胞中的促癌作用，从而调节肿瘤进展。
ABSTRACT N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however β−catenin was increased. Mechanistically, NDRG1 physically associates with TLE2 and β−catenin to affect the Wnt pathway. RNA interference and TLE2 overexpression studies demonstrate that NDRG1 fails to active Wnt pathway compared with isogenic wild-type controls. Strikingly, NDRG1 overexpression induces the epithelial mesenchymal transition (EMT) through activating the Wnt signaling pathway in ESCC cells, decreased the expression of E-cadherin and enhanced the expression of Snail. Our study elucidates a mechanism of NDRG1-regulated Wnt pathway activation and EMT via affecting TLE2 and β-catenin expression in esophageal cancer cells. This indicates a pro-oncogenic role for NDRG1 in esophageal cancer cells whereby it modulates tumor progression.
登录
查看更多内容
影响因子：
3.7
作者：
Mao Z;Sun J;Feng B;Ma J;Zang L;Dong F;Zhang D;Zheng M
通讯作者：
Zheng M
脯氨酰羟化酶抑制剂 3,4-二羟基苯甲酸乙酯通过上调 BNIP3 和 N-myc 下游调节基因 1 诱导食管鳞状细胞癌细胞自噬和凋亡
影响因子：
3.7
作者：
Han B;Li W;Sun Y;Zhou L;Xu Y;Zhao X
通讯作者：
Zhao X
影响因子：
2.6
作者：
Ando, T.;Ishiguro, H.;Kuwabara, Y.
通讯作者：
Kuwabara, Y.
影响因子：
4.7
作者：
Lu, Wen-Jing;Chua, Mei-Sze;So, Samuel K.
通讯作者：
So, Samuel K.
影响因子：
3.6
作者：
Li, Jisheng;Ying, Jianming;Tao, Qian
通讯作者：
Tao, Qian