The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression.

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Bonnomet A,Polette M,Strumane K,Gilles C,Dalstein V,Kileztky C,Berx G,van Roy F,Birembaut P,Nawrocki-Raby B

doi

10.1038/sj.onc.1211035

subject

Has Abstract

pub_date

2008-06-12 00:00:00

pages

3692-9

issue

26

eissn

0950-9232

issn

1476-5594

pii

1211035

journal_volume

27

pub_type

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