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Gd-Metallofullerenol Nanomaterial Suppresses Pancreatic Cancer Metastasis by Inhibiting the Interaction of Histone Deacetylase 1 and Metastasis-Associated Protein 1
Pan, YM; Wang, LM; Kang, SG; Lu, YY; Yang, ZX; Huynh, T; Chen, CY; Zhou, RH; Guo, MZ; Zhao, YL; Zhao YL(赵宇亮)
2015
发表期刊ACS NANO
卷号9期号:7页码:6826-6836
通讯作者赵宇亮
摘要The treatment of pancreatic cancer frequently fails due to local recurrence and hepatic metastasis. Our previous study found that Gd@C-82(OH)(22) can suppress pancreatic cancer by inhibiting MMP-2/9 expression. In this study, we further explored the epigenetic mechanism of Gd@C-82(OH)(22) in human pancreatic cancer metastasis. Gd@C-82(OH)(22) suppressed tumor metastasis through down-regulation of metastasis-associated protein 1 (MTA1), HDAC1, HIF-1 alpha, and MMP-2/9 and up-regulation of reversion-cysteine protein with the Kazal motif (RECK). The level of acetylation was increased in the promoter region of the RECK gene after Gd@C-82(OH)(22) treatment. The interaction of MTA1, HDAC1, and HIF-1 alpha was inhibited by Gd@C-82(OH)(22). Furthermore, large-scale molecular dynamics simulations revealed Gd@C-82(OH)(22) could serve as an effective HDAC inhibitor to the protein protein association between HDAC1 and MTA1, especially through MTA1's SANT and ELM2 dimerization domains. Our findings implicate Gd@C-82(OH)(22) as a novel HDAC inhibitor acting to increase RECK expression by suppressing the MTA1/HDAC1 co-repressor complex. Gd@C-82(OH)(22) may serve as a potential HDAC1 inhibitor to suppress pancreatic cancer cell invasion and metastasis both in vitro and in vivo. According to computer analysis and experimental validation, Gd@C-82(OH)(22) activates RECK expression by inhibiting the interaction of HDAC1 and MTA1.
文章类型Article
关键词pancreatic cancer Gd@C-82(OH)(22) metastasis HDAC1 MTA1 HIF-1 alpha RECK
学科领域Chemistry; Science & Technology - Other Topics; Materials Science
DOI10.1021/nn506782f
收录类别SCI ; EI
WOS类目Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS记录号WOS:000358823200019
引用统计
被引频次:20[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/228687
专题多学科研究中心
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GB/T 7714
Pan, YM,Wang, LM,Kang, SG,et al. Gd-Metallofullerenol Nanomaterial Suppresses Pancreatic Cancer Metastasis by Inhibiting the Interaction of Histone Deacetylase 1 and Metastasis-Associated Protein 1[J]. ACS NANO,2015,9(7):6826-6836.
APA Pan, YM.,Wang, LM.,Kang, SG.,Lu, YY.,Yang, ZX.,...&赵宇亮.(2015).Gd-Metallofullerenol Nanomaterial Suppresses Pancreatic Cancer Metastasis by Inhibiting the Interaction of Histone Deacetylase 1 and Metastasis-Associated Protein 1.ACS NANO,9(7),6826-6836.
MLA Pan, YM,et al."Gd-Metallofullerenol Nanomaterial Suppresses Pancreatic Cancer Metastasis by Inhibiting the Interaction of Histone Deacetylase 1 and Metastasis-Associated Protein 1".ACS NANO 9.7(2015):6826-6836.
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