IHEP OpenIR
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
Source PublicationACS NANO
ISSN1936-0851
EISSN1936-086X
Volume9Issue:7Pages:6826-6836
Corresponding Author赵宇亮
SubtypeArticle
AbstractThe 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.
Keywordpancreatic cancer Gd@C-82(OH)(22) metastasis HDAC1 MTA1 HIF-1 alpha RECK
Subject AreaChemistry; Science & Technology - Other Topics; Materials Science
DOI10.1021/nn506782f
Indexed BySCI ; EI
Language英语
WOS Research AreaChemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS SubjectChemistry ; Science & Technology - Other Topics ; Materials Science
WOS IDWOS:000358823200019
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihep.ac.cn/handle/311005/228687
Collection中国科学院高能物理研究所
Recommended Citation
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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