Regulation of vimentin by SIP1 in human epithelial breast tumor cells.
The expression of Smad interacting protein-1 (SIP1; ZEB2) and the de novo expression of vimentin are frequently involved in epithelial-to-mesenchymal transitions (EMTs) under both normal and pathological conditions. In the present study, we investigated the potential role of SIP1 in the regulation of vimentin during the EMT associated with breast tumor cell migration and invasion. Examining several breast tumor cell lines displaying various degrees of invasiveness, we found SIP1 and vimentin expression only in invasive cell lines. Also, using a model of cell migration with human mammary MCF10A cells, we showed that SIP1 is induced specifically in vimentin-positive migratory cells. Furthermore, transfection of SIP1 cDNA in MCF10A cells increased their vimentin expression both at the mRNA and protein levels and enhanced their migratory abilities in Boyden Chamber assays. Inversely, inhibition of SIP1 expression by RNAi strategies in BT-549 cells and MCF10A cells decreased vimentin expression. We also showed that SIP1 transfection did not activate the TOP-FLASH reporter system, suggesting that the beta-catenin/TCF pathway is not implicated in the regulation of vimentin by SIP1. Our results therefore implicate SIP1 in the regulation of vimentin observed in the EMT associated with breast tumor cell migration, a pathway that may contribute to the metastatic progression of breast cancer.
Bindels
S
S
Laboratory of Tumor and Developmental Biology, Center for Biomedical Integrated Genoproteomics, University of Liège, CHU Sart-Tilman, Liège, Belgium.
Mestdagt
M
M
Vandewalle
C
C
Jacobs
N
N
Volders
L
L
Noël
A
A
van Roy
F
F
Berx
G
G
Foidart
J-M
JM
Gilles
C
C
D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D018076:DNA, Complementary; D005455:Fluorescent Antibody Technique; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010957:Plasmids; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014746:Vimentin / Q000502:physiology*
D017931:DNA Primers; D018076:DNA, Complementary; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D014746:Vimentin