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Autocrine HGF/c-Met signaling pathway confers aggressiveness in lymph node adult T-cell leukemia/lymphoma
http://hdl.handle.net/2237/00033234
http://hdl.handle.net/2237/00033234194f92de-6724-492e-b3e8-cb9851b56a66
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2020-12-23 | |||||
タイトル | ||||||
タイトル | Autocrine HGF/c-Met signaling pathway confers aggressiveness in lymph node adult T-cell leukemia/lymphoma | |||||
言語 | en | |||||
著者 |
Totani, Haruhito
× Totani, Haruhito× Shinjo, Keiko× Suzuki, Miho× Katsushima, Keisuke× Mase, Shoko× Masaki, Ayako× Ito, Asahi× Ri, Masaki× Kusumoto, Shigeru× Komatsu, Hirokazu× Ishida, Takashi× Inagaki, Hiroshi× Iida, Shinsuke× Kondo, Yutaka |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Cytokines | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Histone post-translational modifications | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Leukaemia | |||||
抄録 | ||||||
内容記述 | 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. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
内容記述 | ||||||
内容記述 | ファイル公開:2021/02/27 | |||||
言語 | ja | |||||
内容記述タイプ | Other | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | Springer Nature | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1038/s41388-020-01393-x | |||||
ISSN(print) | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 0950-9232 | |||||
書誌情報 |
en : Oncogene 巻 39, 号 35, p. 5782-5794, 発行日 2020-02-27 |
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著者版フラグ | ||||||
値 | author |