The E-cadherin-repressed hNanos1 gene induces tumor cell invasion by upregulating MT1-MMP expression.
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.
Bonnomet
A
A
INSERM UMRS 514, Laboratory of Histology, IFR 53, CHU Maison Blanche, University of Reims Champagne-Ardenne, Reims, France.
Polette
M
M
Strumane
K
K
Gilles
C
C
Dalstein
V
V
Kileztky
C
C
Berx
G
G
van Roy
F
F
Birembaut
P
P
Nawrocki-Raby
B
B
D015820:Cadherins / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005786:Gene Expression Regulation; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology
D015820:Cadherins; C515170:NANOS1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14