The human NANOS3 gene contributes to lung tumour invasion by inducing epithelial-mesenchymal transition.
Fiche publication
Date publication
septembre 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DALSTEIN Véronique, Pr POLETTE Myriam
Tous les auteurs :
Grelet S, Andries V, Polette M, Gilles C, Staes K, Martin AP, Kileztky C, Terryn C, Dalstein V, Cheng CW, Shen CY, Birembaut P, Van Roy F, Nawrocki-Raby B
Lien Pubmed
Résumé
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.
Référence
J Pathol. 2015 Sep;237(1):25-37