Abstract
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 α6β4 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 α6β4 integrin reduced cell surface expression of this integrin and resulted in decreased invasion of MDA-MB-231 breast carcinoma cells. Interestingly, reduced α6β4 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 β4 expression in these cells augmented the formation of α6β1 heterodimers and increased adhesion to laminin-1. Taken together, these results substantiate the importance of the α6β4 integrin in invasion and migration that has been demonstrated previously by expression of the β4 subunit in β4-deficient cell lines and by function blocking antibodies. Furthermore, these data suggest that the utilization of siRNA oligonucleotides to reduce the expression of the α6β4 integrin may be a useful approach to prevent carcinoma cell progression.
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Lipscomb, E.A., Dugan, A.S., Rabinovitz, I. et al. Use of RNA interference to inhibit integrin (α6β4)-mediated invasion and migration of breast carcinoma cells. Clin Exp Metastasis 20, 569–576 (2003). https://doi.org/10.1023/A:1025819521707
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DOI: https://doi.org/10.1023/A:1025819521707