학술논문

The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression.
Document Type
Article
Source
Oncogene. 6/12/2008, Vol. 27 Issue 26, p3692-3699. 8p. 3 Diagrams, 3 Graphs.
Subject
*TUMORS
*CANCER cells
*MESSENGER RNA
*PROTEINS
*LUNGS
Language
ISSN
0950-9232
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.Oncogene (2008) 27, 3692–3699; doi:10.1038/sj.onc.1211035; published online 28 January 2008 [ABSTRACT FROM AUTHOR]