論文 - 詳細
| RRC ID | 72873 |
|---|---|
| 著者 | Koizumi K, Shintani T, Hayashido Y, Hamada A, Higaki M, Yoshioka Y, Sakamoto A, Yanamoto S, Okamoto T. |
| タイトル | VEGF-A promotes the motility of human melanoma cells through the VEGFR1-PI3K/Akt signaling pathway. |
| ジャーナル | In Vitro Cell Dev Biol Anim |
| Abstract |
Vascular endothelial growth factor A (VEGF-A) and its receptors (VEGFR1 and R2) play important roles in the progression of malignant melanoma through tumor angiogenesis. However, it is not clear whether the VEGF-A/VEGFR1 signaling pathway is involved in the proliferation and migration of melanoma cells. Thus, the effect of VEGF-A on cell migration was investigated in human melanoma cell lines. Of several splicing variants of VEGF-A, VEGF165 is the most abundant and responsible for VEGF-A biological potency. VEGF165 facilitated the migration of melanoma cells in both a chemotactic and chemokinetic manner, but cell proliferation was not affected by VEGF165. VEGF165 also induced the phosphorylation of Akt. In addition, VEGF165-induced cell migration was inhibited significantly by VEGFR1/2 or a VEGFR1-neutralizing antibody. Furthermore, the downregulation of VEGFR1 via the transfection of VEGFR1-targeting antisense oligonucleotides suppressed VEGF165-induced cell migration. Moreover, wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI3K) in the PI3K/Akt pathway, suppressed VEGF165-induced Akt phosphorylation and VEGF165-induced cell migration. These findings suggest that the motility of melanoma cells is regulated by signals mediated through the PI3K/Akt kinase pathway with the activation of VEGFR1 tyrosine kinase by VEGF165. Thus, the downregulation of signaling via VEGF-A/VEGFR1 might be an effective therapeutic approach that could prevent the progression of malignant melanoma. |
| 巻・号 | 58(8) |
| ページ | 758-770 |
| 公開日 | 2022-9-1 |
| DOI | 10.1007/s11626-022-00717-3 |
| PII | 10.1007/s11626-022-00717-3 |
| PMID | 35997849 |
| PMC | PMC9550759 |
| MeSH | Animals Antibodies, Neutralizing / pharmacology Cell Movement / genetics Humans Melanoma* / genetics Oligonucleotides, Antisense / pharmacology Phosphatidylinositol 3-Kinase / metabolism Phosphatidylinositol 3-Kinase / pharmacology Phosphatidylinositol 3-Kinases / metabolism Phosphatidylinositols / pharmacology Proto-Oncogene Proteins c-akt / metabolism Signal Transduction Vascular Endothelial Growth Factor A* / metabolism Wortmannin / pharmacology |
| IF | 1.665 |
| 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 | 5 |
| 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 | SK-MEL-28(RCB1930) G-361(RCB0991) C32TG(RCB1929) |