In silico analysis‐based identification of the target residue of integrin α6 for metastasis inhibition of basal‐like breast cancer. (5th August 2019)

• Record Type: Journal Article
• Authors: Tanaka, Sunao; Senda, Noriko; Iida, Atsuo; Sehara‐Fujisawa, Atsuko; Ishii, Tomoko; Sato, Fumiaki; Toi, Masakazu; Itou, Junji
• Is Part Of: Genes to cells. Volume 24:Number 9(2019)
• Page Start: 596
• Page End: 607
• Publication Date: 2019-08-05
• Subjects: breast cancer -- cell migration -- comparative genomics -- integrin α6 -- peptide; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12714
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract: Metastasis causes death in breast cancer patients. To inhibit breast cancer metastasis, we focused on integrin α6, a membrane protein that contributes to cell migration and metastasis. According to in silico analysis, we identified Asp‐358 as an integrin α6‐specific vertebrate‐conserved residue and consequently as a potential therapeutic target. Because Asp‐358 is located on the surface of the β propeller domain that interacts with other molecules for integrin α6 function, we hypothesized that a peptide with the sequence around Asp‐358 competitively inhibits integrin α6 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 α6 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 α6 function. This study identified the functional residue of integrin α6 and designed the inhibitory peptide. For breast cancer patients, metastasis inhibition therapy may be developed in the future based on this study. Abstract : In silico analyses identified a candidate of the functional residue of integrin α6. A peptide with the sequence around the residue inhibited breast cancer migration and metastasis.