論文 - 詳細
| RRC ID | 62979 |
|---|---|
| 著者 | Totani H, Shinjo K, Suzuki M, Katsushima K, Mase S, Masaki A, Ito A, Ri M, Kusumoto S, Komatsu H, Ishida T, Inagaki H, Iida S, Kondo Y. |
| タイトル | Autocrine HGF/c-Met signaling pathway confers aggressiveness in lymph node adult T-cell leukemia/lymphoma. |
| ジャーナル | Oncogene |
| Abstract |
Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell neoplasm. While ATL cells in peripheral blood (PB-ATL) are sensitive to anti-CC chemokine receptor 4 treatment, non-PB-ATLs, including lymph node ATLs (LN-ATLs), are more aggressive and resistant. We examined characteristic cytokines and growth factors that allow non-PB-ATLs to proliferate and invade compared with PB-ATLs. Protein array analysis revealed hepatocyte growth factor (HGF) and C-C motif chemokine 2 (CCL2) were significantly upregulated in non-PB-ATLs compared with PB-ATLs. The HGF membrane receptor, c-Met, was expressed in PB-ATL and non-PB-ATL cell lines, but CCR2, a CCL2 receptor, was not. Immunohistochemical analysis in clinical ATLs revealed high HGF expression in LNs, pharynx, bone marrow, and tonsils. The HGF/c-Met signaling pathway was active downstream in non-PB-ATLs. Downregulation of HGF/c-Met by siRNA or chemical inhibitors decreased in vitro and in vivo proliferation and invasion by non-PB-ATLs. Treatment with bromodomain and extra-terminal motif inhibitor suppressed HGF expression and decreased levels of histone H3 lysine 27 acetylation (H3K27Ac) and bromodomain-containing protein 4 (BRD4) binding promoter and enhancer regions, suppressing non-PB-ATL cellular growth. Our data indicate H3K27Ac/BRD4 epigenetics regulates the HGF/c-MET pathway in ATLs; targeting this pathway may improve treatment of aggressive non-PB-ATLs. |
| 巻・号 | 39(35) |
| ページ | 5782-5794 |
| 公開日 | 2020-8-1 |
| DOI | 10.1038/s41388-020-01393-x |
| PII | 10.1038/s41388-020-01393-x |
| PMID | 32747750 |
| MeSH | Animals Cell Line, Tumor Hepatocyte Growth Factor / metabolism* Humans Leukemia-Lymphoma, Adult T-Cell / genetics* Lymph Nodes / pathology* Mice Signal Transduction |
| IF | 7.971 |
| 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 | RAW 264(RCB0535) |
| 遺伝子材料 | CSII-CMV-RfA-IRES2-Venus (RDB04388) CSII-CMV-Venus (RDB05553) pENTR4-H1 (RDB04395) CS-RfA-CG (RDB04390) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |