The human NANOS3 gene contributes to lung tumour invasion by inducing epithelial-mesenchymal transition

被引:16
作者
Grelet, Simon [1 ]
Andries, Vanessa [2 ,3 ]
Polette, Myriam [1 ,4 ]
Gilles, Christine [5 ]
Staes, Katrien [2 ,3 ]
Martin, Anne-Pascaline [1 ]
Kileztky, Claire [1 ]
Terryn, Christine [6 ]
Dalstein, Veronique [1 ,4 ]
Cheng, Chun-Wen
Shen, Chen-Yang [7 ]
Birembaut, Philippe [1 ,4 ]
Van Roy, Frans [2 ,3 ]
Nawrocki-Raby, Beatrice [1 ]
机构
[1] Univ Reims, INSERM, UMR S 903, SFR CAP Sante, Champagne Ardenne, France
[2] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium
[3] Inflammat Res Ctr, Mol Cell Biol Unit, Ghent, Belgium
[4] CHU Reims, Histol Lab, Reims, France
[5] Univ Liege, GIGA Canc, Lab Dev & Tumour Biol, B-4000 Liege, Belgium
[6] Univ Reims, Plateforme Imagerie Cellulaire & Tissulaire, Champagne Ardenne, France
[7] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan
关键词
NANOS3; lung cancer; tumour invasion; epithelial-mesenchymal transition; post-transcriptional regulation; SUBCELLULAR-LOCALIZATION; TRANSLATIONAL REGULATION; EUKARYOTIC PROTEINS; DROSOPHILA; EXPRESSION; HUNCHBACK; PUMILIO; CANCER; RNA; RECRUITMENT;
D O I
10.1002/path.4549
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have explored the role of the human NANOS3 gene in lung tumour progression. We show that NANOS3 is over-expressed by invasive lung cancer cells and is a prognostic marker for non-small cell lung carcinomas (NSCLCs). NANOS3 gene expression is restricted in testis and brain and is regulated by epigenetic events. It is up-regulated in cultured cells undergoing epithelial-mesenchymal transition (EMT). NANOS3 over-expression in human NSCLC cell lines enhances their invasiveness by up-regulating EMT, whereas its silencing induces mesenchymal-epithelial transition. NANOS3 represses E-cadherin at the transcriptional level and up-regulates vimentin post-transcriptionally. Also, we show that NANOS3 binds mRNAs encoding vimentin and regulates the length of their poly(A) tail. Finally, NANOS3 can also protect vimentin mRNA from microRNA-mediated repression. We thus demonstrate a role for NANOS3 in the acquisition of invasiveness by human lung tumour cells and propose a new mechanism of post-transcriptional regulation of EMT. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
引用
收藏
页码:25 / 37
页数:13
相关论文
共 43 条
[1]   Epithelial Plasticity: A Common Theme in Embryonic and Cancer Cells [J].
Angela Nieto, M. .
SCIENCE, 2013, 342 (6159) :708-+
[2]   Posttranscriptional regulation by RNA-binding proteins during epithelial-to-mesenchymal transition [J].
Aparicio, Luis A. ;
Abella, Vanessa ;
Valladares, Manuel ;
Figueroa, Angelica .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2013, 70 (23) :4463-4477
[3]   Maternal Pumilio acts together with Nanos in germline development in Drosophila embryos [J].
Asaoka-Taguchi, M ;
Yamada, M ;
Nakamura, A ;
Hanyu, K ;
Kobayashi, S .
NATURE CELL BIOLOGY, 1999, 1 (07) :431-437
[4]   PUMILIO IS ESSENTIAL FOR FUNCTION BUT NOT FOR DISTRIBUTION OF THE DROSOPHILA ABDOMINAL DETERMINANT NANOS [J].
BARKER, DD ;
WANG, C ;
MOORE, J ;
DICKINSON, LK ;
LEHMANN, R .
GENES & DEVELOPMENT, 1992, 6 (12A) :2312-2326
[5]   Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression [J].
Bhandari, Dipankar ;
Raisch, Tobias ;
Weichenrieder, Oliver ;
Jonas, Stefanie ;
Izaurralde, Elisa .
GENES & DEVELOPMENT, 2014, 28 (08) :888-901
[6]   ESLpred: SVM-based method for subcellular localization of eukaryotic proteins using dipeptide composition and PSI-BLAST [J].
Bhasin, M ;
Raghava, GPS .
NUCLEIC ACIDS RESEARCH, 2004, 32 :W414-W419
[7]   Regulation of vimentin by SIP1 in human epithelial breast tumor cells [J].
Bindels, S. ;
Mestdagt, M. ;
Vandewalle, C. ;
Jacobs, N. ;
Volders, L. ;
Noel, A. ;
van Roy, F. ;
Berx, G. ;
Foidart, J-M ;
Gilles, C. .
ONCOGENE, 2006, 25 (36) :4975-4985
[8]   The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression [J].
Bonnomet, A. ;
Polette, M. ;
Strumane, K. ;
Gilles, C. ;
Dalstein, V. ;
Kileztky, C. ;
Berx, G. ;
van Roy, F. ;
Birembaut, P. ;
Nawrocki-Raby, B. .
ONCOGENE, 2008, 27 (26) :3692-3699
[9]   YLoc-an interpretable web server for predicting subcellular localization [J].
Briesemeister, Sebastian ;
Rahnenfuehrer, Joerg ;
Kohlbacher, Oliver .
NUCLEIC ACIDS RESEARCH, 2010, 38 :W497-W502
[10]   SubLoc: a server/client suite for protein subcellular location based on SOAP [J].
Chen, H ;
Huang, N ;
Sun, ZR .
BIOINFORMATICS, 2006, 22 (03) :376-377