Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-β1 expression

被引：39
作者：
Liang, Liang [1 ]
Zeng, Ming [1 ]
Pan, Haixia [1 ]
Liu, Hao [1 ]
He, Yangke [1 ]
机构：
[1] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Canc Ctr, 32 Xierduan Yihuan Rd, Chengdu 611731, Sichuan, Peoples R China
来源：
ONCOLOGY LETTERS | 2018年 / 15卷 / 04期
关键词：
gastric cancer; nicotinamide N-methyltransferase; transforming growth factor-beta 1; epithelial-mesenchymal transition; TUMOR-MARKER; EMT; IDENTIFICATION; PROGNOSIS; PATHWAY; ASSAY;
D O I：
10.3892/ol.2018.7885
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Previous studies have demonstrated that nicotinamide N-methyltransferase (NNMT) is aberrantly expressed in a number of tumors. In the present study, it was demonstrated that the gene and protein levels of NNMT were significantly increased in gastric cancer cells. Furthermore, upregulation of NNMT significantly increased the expression of mesenchymal markers, including a-smooth muscle actin (SMA), vimentin and fibronectin, but decreased the levels of epithelial cadherin. Since transforming growth factor (TGF)-beta 1 may serve a key function in epithelial-mesenchymal transition (EMT), the effects of NNMT on the expression of TGF-beta 1 were investigated in BGC-823 cells. The results demonstrated that overexpression of NNMT significantly induced the expression of TGF-beta 1. However, knockdown of NNMT inhibited the expression of TGF-beta 1, mothers against decapentaplegic homolog (Smad) 2 and alpha-SMA. Additionally, pre-incubation with TGF-beta 1 partially eliminated NNMT-mediated changes in EMT. Collectively, the results demonstrated that upregulation of NNMT in gastric cancer cells may increase the expression of TGF-beta 1, therefore activating TGF-beta 1/Smad signaling, which in turn promotes EMT.
引用
收藏
页码：4592 / 4598
页数：7
相关论文
共 34 条
[1]   The bile acid receptor GPBAR1 (TGR5) is expressed in human gastric cancers and promotes epithelial-mesenchymal transition in gastric cancer cell lines [J].
Carino, Adriana ;
Graziosi, Luigina ;
D'Amore, Claudio ;
Cipriani, Sabrina ;
Marchiano, Silvia ;
Marino, Elisabetta ;
Zampella, Angela ;
Rende, Mario ;
Mosci, Paolo ;
Distrutti, Eleonora ;
Donini, Annibale ;
Fiorucci, Stefano .
ONCOTARGET, 2016, 7 (38) :61021-61035
[2]  
Chen C, 2016, AM J CANCER RES, V6, P649
[3]   Galectin-1 induces invasion and the epithelial-mesenchymal transition in human gastric cancer cells via non-canonical activation of the hedgehog signaling pathway [J].
Chong, Yang ;
Tang, Dong ;
Gao, Jun ;
Jiang, Xuetong ;
Xu, Chuanqi ;
Xiong, Qingquan ;
Huang, Yuqin ;
Wang, Jie ;
Zhou, Huaicheng ;
Shi, Youquan ;
Wang, Daorong .
ONCOTARGET, 2016, 7 (50) :83611-83626
[4]   Galectin-1 from cancer-associated fibroblasts induces epithelial-mesenchymal transition through β1 integrin-mediated upregulation of Gli1 in gastric cancer [J].
Chong, Yang ;
Tang, Dong ;
Xiong, Qingquan ;
Jiang, Xuetong ;
Xu, Chuanqi ;
Huang, Yuqin ;
Wang, Jie ;
Zhou, Huaicheng ;
Shi, Youquan ;
Wu, Xiaoqing ;
Wang, Daorong .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2016, 35 :1-13
[5]   Asparaginyl endopeptidase promotes the invasion and metastasis of gastric cancer through modulating epithelial-to-mesenchymal transition and analysis of their phosphorylation signaling pathways [J].
Cui, Yuehong ;
Wang, Yan ;
Li, Hong ;
Li, Qian ;
Yu, Yiyi ;
Xu, Xiaojing ;
Xu, Bei ;
Liu, Tianshu .
ONCOTARGET, 2016, 7 (23) :34356-34370
[6]   Gastrokine-2 suppresses epithelial mesenchymal transition through PI3K/AKT/GSK3β signaling in gastric cancer [J].
Dai, Jin ;
Qian, Chenchen ;
Su, Mingli ;
Chen, Minhu ;
Chen, Jie .
TUMOR BIOLOGY, 2016, 37 (09) :12403-12410
[7]   HOXB8 promotes tumor metastasis and the epithelial-mesenchymal transition via ZEB2 targets in gastric cancer [J].
Ding, Wen-Jin ;
Zhou, Min ;
Chen, Mei-Mei ;
Qu, Chun-Ying .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2017, 143 (03) :385-397
[8]   Loss of GFAT1 promotes epithelial-to-mesenchymal transition and predicts unfavorable prognosis in gastric cancer [J].
Duan, Fangfang ;
Jia, Dongwei ;
Zhao, Junjie ;
Wu, Weicheng ;
Min, Lingqiang ;
Song, Shushu ;
Wu, Hao ;
Wang, Lan ;
Wang, Hongshan ;
Ruan, Yuanyuan ;
Gu, Jianxin .
ONCOTARGET, 2016, 7 (25) :38427-38439
[9]   RETRACTED: Decreased expression of the long noncoding RNA LINC00261 indicate poor prognosis in gastric cancer and suppress gastric cancer metastasis by affecting the epithelial-mesenchymal transition(Retracted article. See vol. 11, art no 2, 2018) [J].
Fan, Yu ;
Wang, Yan-fen ;
Su, Hua-fang ;
Fang, Na ;
Zou, Chen ;
Li, Wen-feng ;
Fei, Zheng-hua .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2016, 9
[10]   Activation of the nicotinamide N-methyltransferase (NNMT)-1-methylnicotinamide (MNA) pathway in pulmonary hypertension [J].
Fedorowicz, Andrzej ;
Mateuszuk, Lukasz ;
Kopec, Grzegorz ;
Skorka, Tomasz ;
Kutryb-Zajac, Barbara ;
Zakrzewska, Agnieszka ;
Walczak, Maria ;
Jakubowski, Andrzej ;
Lomnicka, Magdalena ;
Slominska, Ewa ;
Chlopicki, Stefan .
RESPIRATORY RESEARCH, 2016, 17
1234