The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression.
Fiche publication
Date publication
juin 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DALSTEIN Véronique, Pr POLETTE Myriam
Tous les auteurs :
Bonnomet A, Polette M, Strumane K, Gilles C, Dalstein V, Kileztky C, Berx G, van Roy F, Birembaut P, Nawrocki-Raby B
Lien Pubmed
Résumé
In this study, we examined the role of the E-cadherin-repressed gene human Nanos1 (hNanos1) in tumor invasion process. First, our in vivo study revealed that hNanos1 mRNAs were overexpressed in invasive lung carcinomas. Moreover, hNanos1 was co-localized with MT1-MMP (membrane type 1-matrix metalloproteinase) in E-cadherin-negative invasive lung tumor clusters. Using an inducible Tet-on system, we showed that induction of hNanos1 expression in DLD1 cells increased their migratory and invasive abilities in a three-dimensional migration and in a modified Boyden chamber assay. Accordingly, we demonstrated that hNanos1 upregulated MT1-MMP expression at the mRNA and protein levels. Inversely, using an RNA interference strategy to inhibit hNanos1 expression in invasive Hs578T, BT549 and BZR cancer cells, we observed a downregulation of MT1-MMP mRNA and protein and concomitantly a decrease of the invasive capacities of tumor cells in a modified Boyden chamber assay. Taken together, our results demonstrate that hNanos1, by regulating MT1-MMP expression, plays an important role in the acquisition of invasive properties by epithelial tumor cells.
Référence
Oncogene. 2008 Jun 12;27(26):3692-9