Deficiency of pigment epithelium-derived factor in nasopharyngeal carcinoma cells triggers the epithelial-mesenchymal transition and metastasis.
Deficiency of pigment epithelium-derived factor in nasopharyngeal carcinoma cells triggers the epithelial-mesenchymal transition and metastasis.
复制标题
鼻咽癌细胞色素上皮衍生因子缺乏引发上皮间质转化和转移
DOI：
10.1038/cddis.2017.114
复制
发表时间：
2017-06-01
影响因子：
9
通讯作者：
Gao G
中科院分区：
文献类型：
--
作者：
Zhang T;Yin P;Zhang Z;Xu B;Che D;Dai Z;Dong C;Jiang P;Hong H;Yang Z;Zhou T;Shao J;Xu Z;Yang X;Gao G
远处转移是鼻咽癌治疗失败的主要原因，而上皮-间充质转化(EMT)是鼻咽癌侵袭转移的关键过程。然而，与癌基因相比，参与鼻咽癌EMT和转移的抑癌基因的研究还不是很清楚。在本研究中，一种强大的内源性抗肿瘤因子--色素上皮源性因子(PEDF)在人鼻咽癌组织中的表达减弱，并与临床病理和EMT特征有关。在低转移的鼻咽癌细胞系中，PEDF基因的敲除诱导了EMT，而在具有典型EMT的高转移鼻咽癌细胞系中，PEDF的过表达恢复了上皮细胞的表型。PEDF对鼻咽癌细胞自发性转移的体内抑制作用提示LRP6/GSK3AKT-连环蛋白信号通路而不是β/β/GSK3AKT/β信号通路参与了PEDF对EMT的影响。MiR-320C升高可直接下调鼻咽癌中PEDF的表达。综上所述，我们的研究结果首次表明PEDF在鼻咽癌EMT的发生和转移中起到了抑癌基因的作用。PEDF可作为鼻咽癌诊断、预后和治疗的候选指标。
Distant metastasis is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure while epithelial–mesenchymal transition (EMT) is the critical process of NPC invasion and metastasis. However, tumor-suppressor genes involved in the EMT and metastasis of NPC have not been explored clearly compared with the oncogenes. In the present study, the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antitumor factor, was diminished in human NPC tissues and associated with clinicopathological and EMT features. The knockdown of PEDF induced EMT in lower metastatic NPC cell lines and overexpression of PEDF restored epithelial phenotype in higher metastatic NPC cell lines with typical EMT. The inhibition of PEDF mediated NPC cell spontaneous metastasis in vivo. LRP6/GSK3β/β-catenin signal pathway rather than AKT/GSK3β pathway was involved in the effects of PEDF on EMT. The expression of PEDF was directly downregulated by elevated miR-320c in NPC. In conclusion, our findings indicate for the first time that PEDF functions as tumor-suppressor gene in the occurrence of EMT and metastasis in NPC. PEDF could serve as a promising candidate for NPC diagnosis, prognosis and treatment.
登录
查看更多内容
DOI：
10.1186/s13046-015-0278-7
发表时间：
2016-01-08
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Belkacemi L;Zhang SX
通讯作者：
Zhang SX
影响因子：
5.3
作者：
Park, Kyoungmin;Lee, Kyungwon;Ma, Jian-xing
通讯作者：
Ma, Jian-xing
影响因子：
6.7
作者：
Kong QL;Hu LJ;Cao JY;Huang YJ;Xu LH;Liang Y;Xiong D;Guan S;Guo BH;Mai HQ;Chen QY;Zhang X;Li MZ;Shao JY;Qian CN;Xia YF;Song LB;Zeng YX;Zeng MS
通讯作者：
Zeng MS
影响因子：
3.4
作者：
Becerra, SP;Fariss, RN;Pfeffer, BA
通讯作者：
Pfeffer, BA
SFRP1 低表达与不良预后相关，并通过激活 NPC 中的 Wnt/β-Catenin 信号通路促进细胞侵袭
影响因子：
3.3
作者：
Ren, Xian-Yue;Zhou, Guan-Qun;Ma, Jun
通讯作者：
Ma, Jun