NDRG1 attenuates epithelial-mesenchymal transition of nasopharyngeal cancer cells via blocking Smad2 signaling

被引:30
作者
Hu, Zhi-Yan [1 ,2 ]
Xie, Wei-Bing [3 ]
Yang, Fang [1 ,2 ]
Xiao, Li-Wei [1 ,2 ]
Wang, Xiao-Yan [1 ,2 ]
Chen, Shi-You [4 ]
Li, Zu-Guo [1 ,2 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China
[2] Southern Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou 510515, Guangdong, Peoples R China
[3] Southern Med Univ, Sch Basic Med Sci, Dept Forens Sci, Guangzhou 510515, Guangdong, Peoples R China
[4] Univ Georgia, Dept Physiol & Pharmacol, Athens, GA 30602 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2015年 / 1852卷 / 09期
基金
中国国家自然科学基金; 美国国家卫生研究院;
关键词
N-myc downstream-regulated gene 1; Nasopharyngeal carcinoma; Proliferation; Metastasis; Epithelial-mesenchymal transition; REGULATED GENE-1 NDRG1; SUPPRESSES TUMOR-GROWTH; POOR-PROGNOSIS; METASTASIS SUPPRESSOR; HEPATOCELLULAR-CARCINOMA; TGF-BETA; DECREASED EXPRESSION; PANCREATIC-CANCER; OVARIAN-CANCER; BREAST-CANCER;
D O I
10.1016/j.bbadis.2015.06.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
N-myc downstream-regulated gene 1 (NDRG1) has been implicated in tumorigenesis and metastasis in different cancers. However, its role in nasopharyngeal carcinoma remains unknown. We found that NDRG1 expression level was high in nasopharyngeal cancer 5-8F cells but low in 5-8F-LN cells with lymphatic metastasis potential. Knockdown of NDRG1 by shRNA promoted 5-8F cell proliferation, migration, and invasion in vitro and its tumorigenesis in vivo. Moreover, NDRG1 deficiency induced an epithelial-mesenchymal transition (EMT) of 5-8F cells as shown by an attenuation of E-cadherin and an induction of N-cadherin and vimentin expression. NDRG1 knockdown also enhanced Smad2 expression and phosphorylation. Smad2 signaling was attenuated in 5-8F cells but was significantly activated in 5-8F-LN cells. Knockdown of Smad2 restored E-cadherin but attenuated N-cadherin expression in NDRG1-deficient 5-8F cells, suggesting a reduction of EMT. Consistently, blockade of Smad2 in 5-8F-LN cells increased E-cadherin while diminishing N-cadherin and vimentin expression. These data indicate that Smad2 mediates the NDRG1 deficiency-induced EMT of 5-8F cells. In tumors derived from NDRG1-deficient 5-8F cells, E-cadherin expression was inhibited while vimentin and Smad2 were increased in a large number of cancer cells. Most importantly, NDRG1 expression was attenuated in human nasopharyngeal carcinoma tissues, resulted in a lower survival rate in patients. The NDRG1 was further decreased in the detached nasopharyngeal cancer cells, which was associated with a further reduced survival rate in patients with lymphatic metastasis. Taken together, these results demonstrated that NDRG1 prevents nasopharyngeal tumorigenesis and metastasis via inhibiting Smad2-mediated EMT of nasopharyngeal cells. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:1876 / 1886
页数:11
相关论文
共 50 条
[1]  
Abbasi AN, 2011, ASIAN PAC J CANCER P, V12, P735
[2]   N-myc downstream regulated gene1/Cap43 overexpression suppresses tumor growth by hepatic cancer cells through cell cycle arrest at the G0/G1 phase [J].
Akiba, Jun ;
Murakami, Yuichi ;
Noda, Masaki ;
Watari, Kosuke ;
Ogasawara, Sachiko ;
Yoshida, Takafumi ;
Kawahara, Akihiko ;
Sanada, Sakiko ;
Yasumoto, Makiko ;
Yamaguchi, Rin ;
Kage, Masayoshi ;
Kuwano, Michihiko ;
Ono, Mayumi ;
Yano, Hirohisa .
CANCER LETTERS, 2011, 310 (01) :25-34
[3]   N-myc downstream regulated gene 1 (NDRG1)/Cap43 enhances portal vein invasion and intrahepatic metastasis in human hepatocellular carcinoma [J].
Akiba, Jun ;
Ogasawara, Sachiko ;
Kawahara, Akihiko ;
Nishida, Naoyo ;
Sanada, Sakiko ;
Moriya, Fukuko ;
Kuwano, Michihiko ;
Nakashima, Osamu ;
Yano, Hirohisa .
ONCOLOGY REPORTS, 2008, 20 (06) :1329-1335
[4]   Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma [J].
Ando, T. ;
Ishiguro, H. ;
Kimura, M. ;
Mitsui, A. ;
Kurehara, H. ;
Sugito, N. ;
Tomoda, K. ;
Mori, R. ;
Takashima, N. ;
Ogawa, R. ;
Fujii, Y. ;
Kuwabara, Y. .
DISEASES OF THE ESOPHAGUS, 2006, 19 (06) :454-458
[5]   Nox4 involvement in TGF-beta and SMAD3-driven induction of the epithelial-to-mesenchymal transition and migration of breast epithelial cells [J].
Boudreau, Howard E. ;
Casterline, Benjamin W. ;
Rada, Balazs ;
Korzeniowska, Agnieszka ;
Leto, Thomas L. .
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 53 (07) :1489-1499
[6]   NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells [J].
Chang, Xiaojing ;
Xu, Xiaoyang ;
Ma, Jinguo ;
Xue, Xiaoying ;
Li, Zhenhua ;
Deng, Peng ;
Zhang, Shuanglong ;
Zhi, Yu ;
Chen, Jing ;
Dai, Dongqiu .
MOLECULAR BIOLOGY REPORTS, 2014, 41 (09) :6215-6223
[7]   The Iron Chelators Dp44mT and DFO Inhibit TGF-β-induced Epithelial-Mesenchymal Transition via Up-Regulation of N-Myc Downstream-regulated Gene 1 (NDRG1) [J].
Chen, Zhiqiang ;
Zhang, Daohai ;
Yue, Fei ;
Zheng, Minhua ;
Kovacevic, Zaklina ;
Richardson, Des R. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (21) :17016-17028
[8]   NDRG1 as a biomarker for metastasis, recurrence and of poor prognosis in hepatocellular carcinoma [J].
Cheng, Jun ;
Xie, Hai-Yang ;
Xu, Xiao ;
Wu, Jian ;
Wei, Xuyong ;
Su, Rong ;
Zhang, Wu ;
Lv, Zhen ;
Zheng, Shusen ;
Zhou, Lin .
CANCER LETTERS, 2011, 310 (01) :35-45
[9]   Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma [J].
Chua, Mei-Sze ;
Sun, Hongbo ;
Cheung, Siu T. ;
Mason, Veronica ;
Higgins, John ;
Ross, Douglas T. ;
Fan, Sheung T. ;
So, Samuel .
MODERN PATHOLOGY, 2007, 20 (01) :76-83
[10]   Signaling pathway cooperation in TGF-β-induced epithelial-mesenchymal transition [J].
Derynck, Rik ;
Muthusamy, Baby Periyanayaki ;
Saeteurn, Koy Y. .
CURRENT OPINION IN CELL BIOLOGY, 2014, 31 :56-66