PUBLICATION
In silico analysis-based identification of the target residue of integrin α6 for metastasis inhibition of basal-like breast cancer
- Authors
- Tanaka, S., Senda, N., Iida, A., Sehara-Fujisawa, A., Ishii, T., Sato, F., Toi, M., Itou, J.
- ID
- ZDB-PUB-200110-21
- Date
- 2019
- Source
- Genes to cells : devoted to molecular & cellular mechanisms 24: 596-607 (Journal)
- Registered Authors
- Ishii, Tomohiro, Sehara-Fujisawa, Atsuko
- Keywords
- breast cancer, cell migration, comparative genomics, integrin α6, peptide
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/pharmacology*
- Asparagine/chemistry
- Asparagine/genetics
- Breast Neoplasms/metabolism*
- Breast Neoplasms/pathology
- Cell Movement/drug effects*
- Conserved Sequence
- Female
- Focal Adhesions/drug effects
- Humans
- Integrin alpha6/chemistry
- Integrin alpha6/genetics
- Integrin alpha6/metabolism*
- MCF-7 Cells
- Mice
- Mice, Nude
- Neoplasm Metastasis
- Peptide Fragments/chemistry
- Peptide Fragments/pharmacology*
- Protein Binding/drug effects
- Protein Domains
- Zebrafish
- PubMed
- 31295752 Full text @ Genes Cells
Citation
Tanaka, S., Senda, N., Iida, A., Sehara-Fujisawa, A., Ishii, T., Sato, F., Toi, M., Itou, J. (2019) In silico analysis-based identification of the target residue of integrin α6 for metastasis inhibition of basal-like breast cancer. Genes to cells : devoted to molecular & cellular mechanisms. 24:596-607.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping