https://scholars.lib.ntu.edu.tw/handle/123456789/191025
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor | 臺大醫學院-內科;臺大醫學院-病理學科暨研究所; | - |
dc.contributor.author | Lin, Ching-Wen | en_US |
dc.contributor.author | Wang, Lu-Kai | en_US |
dc.contributor.author | Wang, Shu-Ping | en_US |
dc.contributor.author | Chang, Yi-Liang | en_US |
dc.contributor.author | Wu, Yi-Ying | en_US |
dc.contributor.author | Chen, Hsuan-Yu | en_US |
dc.contributor.author | Hsiao, Tzu-Hung | en_US |
dc.contributor.author | Lai, Wei-Yun | en_US |
dc.contributor.author | Lu, Hsuan-Hsuan | en_US |
dc.contributor.author | Chang, Ya-Hsuan | en_US |
dc.contributor.author | Yang, Shuenn-Chen | en_US |
dc.contributor.author | Lin, Ming-Wei | en_US |
dc.contributor.author | Chen, Chi-Yuan | en_US |
dc.contributor.author | Hong, Tse-Ming | en_US |
dc.contributor.author | PAN-CHYR YANG | en_US |
dc.creator | Lin, Ching-Wen;Wang, Lu-Kai;Wang, Shu-Ping;Chang, Yi-Liang;Wu, Yi-Ying;Chen, Hsuan-Yu;Hsiao, Tzu-Hung;Lai, Wei-Yun;Lu, Hsuan-Hsuan;Chang, Ya-Hsuan;Yang, Shuenn-Chen;Lin, Ming-Wei;Chen, Chi-Yuan;Hong, Tse-Ming;Yang, Pan-Chyr | en |
dc.creator | 張逸良;楊泮池 | zh-tw |
dc.date | 2016 | - |
dc.date.accessioned | 2017-04-25T11:02:18Z | - |
dc.date.accessioned | 2018-07-11T07:11:46Z | - |
dc.date.available | 2017-04-25T11:02:18Z | - |
dc.date.available | 2018-07-11T07:11:46Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://ntur.lib.ntu.edu.tw//handle/246246/278807 | - |
dc.description.abstract | Hypoxia is a major driving force of cancer invasion and metastasis. Here we show that death domain-associated protein (Daxx) acts to negatively regulate hypoxia-induced cell dissemination and invasion by inhibiting the HIF-1 alpha/HDAC1/Slug pathway. Daxx directly binds to the DNA-binding domain of Slug, impeding histone deacetylase 1 (HDAC1) recruitment and antagonizing Slug E-box binding. This, in turn, stimulates E-cadherin and occludin expression and suppresses Slug-mediated epithelial-mesenchymal transition (EMT) and cell invasiveness. Under hypoxic conditions, stabilized hypoxia-inducible factor (HIF)-1 alpha downregulates Daxx expression and promotes cancer invasion, whereas re-expression of Daxx represses hypoxia-induced cancer invasion. Daxx also suppresses Slug-mediated lung cancer metastasis in an orthotopic lung metastasis mouse model. Using clinical tumour samples, we confirmed that the HIF-1 alpha/Daxx/Slug pathway is an outcome predictor. Our results support that Daxx can act as a repressor in controlling HIF-1 alpha/HDAC1/Slug-mediated cancer cell invasion and is a potential therapeutic target for inhibition of cancer metastasis. | en_US |
dc.language | en-us | - |
dc.relation | Nat. Commun., 7, | en_US |
dc.relation.ispartof | Nat. Commun. | en_US |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | Daxx protein; histone deacetylase 1; hypoxia inducible factor 1alpha; messenger RNA; occludin; transcription factor Slug; uvomorulin; DAXX protein, human; HDAC1 protein, human; HIF1A protein, human; histone deacetylase 1; hypoxia inducible factor 1alpha; nuclear protein; protein binding; signal transducing adaptor protein; SNAI1 protein, human; transcription factor Snail; transcriptome; tumor suppressor protein; cancer; cells and cell components; enzyme activity; gene expression; hypoxia; inhibition; numerical model; protein; rodent; tumor; animal experiment; animal model; animal tissue; Article; cancer patient; cancer prognosis; cancer survival; cellular distribution; comparative study; controlled study; down regulation; E box element; epithelial mesenchymal transition; gene expression; human; human cell; human tissue; hypoxia; in vivo study; lung cancer cell line; lung carcinogenesis; lung metastasis; major clinical study; male; metastasis inhibition; migration inhibition; mouse; non small cell lung cancer; nonhuman; overall survival; promoter region; protein expression; protein function; protein protein interaction; signal transduction; transcription regulation; tumor invasion; zinc finger motif; animal; Bagg albino mouse; biological model; chemistry; genetics; lung tumor; metabolism; nonobese diabetic mouse; nude mouse; physiology; prevention and control; protein domain; SCID mouse; secondary; tumor cell line; tumor hypoxia; tumor invasion; Adaptor Proteins, Signal Transducing; Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Epithelial-Mesenchymal Transition; Histone Deacetylase 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mice, Nude; Mice, SCID; Models, Biological; Neoplasm Invasiveness; Nuclear Proteins; Protein Binding; Protein Interaction Domains and Motifs; Signal Transduction; Snail Family Transcription Factors; Transcriptome; Tumor Hypoxia; Tumor Suppressor Proteins | - |
dc.title | Daxx inhibits hypoxia-induced lung cancer cell metastasis by suppressing the HIF-1α/HDAC1/Slug axis | en_US |
dc.identifier.doi | 10.1038/ncomms13867 | - |
dc.relation.pages | - | en_US |
dc.relation.journalissue | 7 | en_US |
item.grantfulltext | none | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Internal Medicine | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Clinical Pharmacy | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Biomedical Electronics and Bioinformatics | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.orcid | 0000-0001-6330-6048 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Electrical Engineering and Computer Science | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 醫學系 |
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