In silico analysis-based identification of the target residue of integrin α6 for metastasis inhibition of basal-like breast cancer.
Animals
Antineoplastic Agents
/ chemistry
Asparagine
/ chemistry
Breast Neoplasms
/ metabolism
Cell Movement
/ drug effects
Conserved Sequence
Female
Focal Adhesions
/ drug effects
Humans
Integrin alpha6
/ chemistry
MCF-7 Cells
Mice
Mice, Nude
Neoplasm Metastasis
Peptide Fragments
/ chemistry
Protein Binding
/ drug effects
Protein Domains
Zebrafish
breast cancer
cell migration
comparative genomics
integrin α6
peptide
Journal
Genes to cells : devoted to molecular & cellular mechanisms
ISSN: 1365-2443
Titre abrégé: Genes Cells
Pays: England
ID NLM: 9607379
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
04
02
2019
revised:
04
07
2019
accepted:
08
07
2019
pubmed:
12
7
2019
medline:
10
1
2020
entrez:
12
7
2019
Statut:
ppublish
Résumé
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.
Substances chimiques
Antineoplastic Agents
0
Integrin alpha6
0
Peptide Fragments
0
Asparagine
7006-34-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
596-607Subventions
Organisme : Taiho Pharmaceutical
Informations de copyright
© 2019 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
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