論文 - 詳細
| RRC ID | 45065 |
|---|---|
| 著者 | Tanaka R, Seki Y, Saito Y, Kamiya S, Fujita M, Okutsu H, Iyoda T, Takai T, Owaki T, Yajima H, Taira J, Hayashi R, Kodama H, Matsunaga T, Fukai F. |
| タイトル | Tenascin-C-derived peptide TNIIIA2 highly enhances cell survival and platelet-derived growth factor (PDGF)-dependent cell proliferation through potentiated and sustained activation of integrin α5β1. |
| ジャーナル | J Biol Chem |
| Abstract |
Tenascin-C is an adhesion modulatory matrix protein that is highly expressed in tumors; however, its biochemical activity involved in tumorigenesis is not fully understood. On the other hand, increasing evidence indicates the importance of integrin α5β1 in cancer development. We previously demonstrated that tenascin-C harbors a functional site that can be released as a proadhesive peptide such as TNIIIA2. Peptide TNIIIA2 is capable of inducing activation of β1-integrins including α5β1 via syndecan-4. In this study the proadhesive effect of TNIIIA2 was characterized by potentiated and sustained activation of integrin α5β1. Based on this effect, TNIIIA2 rendered nontransformed fibroblasts (NIH3T3) resistant to serum deprivation-elicited anoikis through activation of the Akt/Bcl-2 pathway. Moreover, TNIIIA2 hyperstimulated PDGF-dependent proliferation of NIH3T3 by activating integrin α5β1. Tenascin-C, a parental protein of TNIIIA2, also stimulated PDGF-dependent proliferation, which was blocked by a matrix metalloproteinase-2/9 inhibitor and an anti-TNIIIA2 function-blocking antibody, suggesting proteolytic exposure of the proadhesive effect of TNIIIA2. Mechanistic analyses revealed that TNIIIA2 induced a lateral association of PDGF receptor β with the molecular complex of activated integrin α5β1 and syndecan-4 in the membrane microdomains enriched with cholesterol/caveolin-1, resulting in prolonged activation of PDGF receptor β and the subsequent Ras/mitogen-activated protein kinase pathway in a PDGF-dependent manner. Of note, TNIIIA2 induced continuous proliferation in NIH3T3 in an integrin α5β1-dependent manner even after they formed a confluent monolayer. Thus, it was proposed that tenascin-C might be involved in deregulated cell growth through potentiated and sustained activation of integrin α5β1 after exposure of the proadhesive effect of TNIIIA2. |
| 巻・号 | 289(25) |
| ページ | 17699-708 |
| 公開日 | 2014-6-20 |
| DOI | 10.1074/jbc.M113.546622 |
| PII | S0021-9258(20)40610-6 |
| PMID | 24808173 |
| PMC | PMC4067204 |
| MeSH | Animals Cell Proliferation / drug effects* Cell Survival / drug effects Humans K562 Cells Membrane Microdomains / genetics Membrane Microdomains / metabolism Mice NIH 3T3 Cells Peptides / chemistry Peptides / pharmacology* Platelet-Derived Growth Factor / genetics Platelet-Derived Growth Factor / metabolism* Receptor, Platelet-Derived Growth Factor beta / genetics Receptor, Platelet-Derived Growth Factor beta / metabolism Receptors, Vitronectin / genetics Receptors, Vitronectin / metabolism* Syndecan-4 / genetics Syndecan-4 / metabolism Tenascin / chemistry Tenascin / pharmacology* |
| IF | 4.238 |
| 引用数 | 20 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | K562 |