Use of RNA interference to inhibit integrin (alpha6beta4)-mediated invasion and migration of breast carcinoma cells
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2003-11-06Keywords
BiotinylationBreast Neoplasms
Cell Adhesion
Cell Movement
Dimerization
Female
Gene Silencing
Humans
Integrin alpha6beta4
Laminin
Neoplasm Invasiveness
RNA, Small Interfering
Tumor Cells, Cultured
α6β4
adhesion
integrin
invasion
ligand-independent
migration
small interfering RNA
RNA interference
Amino Acids, Peptides, and Proteins
Cancer Biology
Cells
Chemical Actions and Uses
Neoplasms
Nucleic Acids, Nucleotides, and Nucleosides
Skin and Connective Tissue Diseases
Metadata
Show full item recordAbstract
The application of small interfering RNA (siRNA) oligonucleotides to silence gene expression has profound implications for the intervention of human diseases including cancer. Using this technique, we explored the possibility that the alpha6beta4 integrin, a laminin adhesion receptor with a recognized role in the invasive phenotype of many carcinomas, represents a potential therapeutic target to inhibit the migration and invasion of carcinoma cells. We found that siRNA oligonucleotides targeted to either subunit of the alpha6beta4 integrin reduced cell surface expression of this integrin and resulted in decreased invasion of MDA-MB-231 breast carcinoma cells. Interestingly, reduced alpha6beta4 expression also promoted decreased migration on non-laminin substrata indicating that this integrin can function in a ligand-independent manner. In addition, the absence of beta4 expression in these cells augmented the formation of alpha6beta1 heterodimers and increased adhesion to laminin-1. Taken together, these results substantiate the importance of the alpha6beta4 integrin in invasion and migration that has been demonstrated previously by expression of the beta4 subunit in beta4-deficient cell lines and by function blocking antibodies. Furthermore, these data suggest that the utilization of siRNA oligonucleotides to reduce the expression of the alpha6beta4 integrin may be a useful approach to prevent carcinoma cell progression.Source
Clin Exp Metastasis. 2003;20(6):569-76.
DOI
10.1023/a:1025819521707Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26252PubMed ID
14598892Related Resources
ae974a485f413a2113503eed53cd6c53
10.1023/a:1025819521707