In silico analysis-based identification of the target residue of integrin α6 for metastasis inhibition of basal-like breast cancer

Metastasis causes death in breast cancer patients. To inhibit breast cancer metastasis, we focused on integrin alpha 6, a membrane protein that contributes to cell migration and metastasis. According to in silico analysis, we identified Asp-358 as an integrin alpha 6-specific vertebrate-conserved residue and consequently as a potential therapeutic target. Because Asp-358 is located on the surface of the beta propeller domain that interacts with other molecules for integrin alpha 6 function, we hypothesized that a peptide with the sequence around Asp-358 competitively inhibits integrin alpha 6 complex formation. We treated basal-like breast cancer cells with the peptide and observed reductions in cell migration and metastasis. The result of the immunoprecipitation assay showed that the peptide inhibited integrin alpha 6 complex formation. Our immunofluorescence for phosphorylated paxillin, a marker of integrin-regulated focal adhesion, showed that the peptide reduced the number of focal adhesions. These results indicate that the peptide inhibits integrin alpha 6 function. This study identified the functional residue of integrin alpha 6 and designed the inhibitory peptide. For breast cancer patients, metastasis inhibition therapy may be developed in the future based on this study.