https://scholars.lib.ntu.edu.tw/handle/123456789/582956
標題: | GATA3 interacts with and stabilizes HIF-1α to enhance cancer cell invasiveness | 作者: | MEI-CHUN LIN JING-JER LIN CHIA-LANG HSU Juan H.-F. PEI-JEN LOU MIN-CHUAN HUANG |
公開日期: | 2017 | 出版社: | Nature Publishing Group | 卷: | 36 | 期: | 30 | 起(迄)頁: | 4243-4252 | 來源出版物: | Oncogene | 摘要: | GATA binding protein 3 (GATA3) is indispensable in development of human organs. However, the role of GATA3 in cancers remains elusive. Hypoxia inducible factor (HIF)-1 plays an important role in pathogenesis of human cancers. Regulation of HIF-1α degradation is orchestrated through collaboration of its interacting proteins. In this study, we discover that GATA3 is upregulated in head and neck squamous cell carcinoma (HNSCC) and is an independent predictor for poor disease-free survival. GATA3 promotes invasive behaviours of HNSCC and melanoma cells in vitro and in immunodeficient mice. Mechanistically, GATA3 physically associates with HIF-1α under hypoxia to inhibit ubiquitination and proteasomal degradation of HIF-1α, which is independent of HIF-1α prolyl hydroxylation. Chromatin immunoprecipitation assays show that the GATA3/HIF-1α complex binds to and regulates HIF-1 target genes, which is also supported by the microarray analysis. Notably, the GATA3-mediated invasiveness can be significantly reversed by HIF-1α knockdown, suggesting a critical role of HIF-1α in the underlying mechanism of GATA3-mediated effects. Our findings suggest that GATA3 stabilizes HIF-1α to enhance cancer invasiveness under hypoxia and support the GATA3/HIF-1α axis as a potential therapeutic target for cancer treatment. ? 2017 The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014550183&doi=10.1038%2fonc.2017.8&partnerID=40&md5=3a4400b9cd236bb7547415f3004fb37f https://scholars.lib.ntu.edu.tw/handle/123456789/582956 |
ISSN: | 0950-9232 | DOI: | 10.1038/onc.2017.8 | SDG/關鍵字: | hypoxia inducible factor 1alpha; transcription factor GATA 3; GATA3 protein, human; HIF1A protein, human; hypoxia inducible factor 1alpha; transcription factor GATA 3; adult; animal experiment; animal model; animal tissue; Article; chromatin immunoprecipitation; complex formation; disease free survival; female; gene; head and neck squamous cell carcinoma; human; human tissue; hydroxylation; in vitro study; male; melanoma cell; microarray analysis; middle aged; mouse; nonhuman; priority journal; protein degradation; protein protein interaction; protein stability; tumor invasion; ubiquitination; upregulation; animal; cell hypoxia; gene expression regulation; head and neck tumor; immunohistochemistry; immunoprecipitation; metabolism; nonobese diabetic mouse; pathology; physiology; real time polymerase chain reaction; SCID mouse; squamous cell carcinoma; tumor invasion; Western blotting; xenograft; Animals; Blotting, Western; Carcinoma, Squamous Cell; Cell Hypoxia; Chromatin Immunoprecipitation; Female; GATA3 Transcription Factor; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Heterografts; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Immunoprecipitation; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Invasiveness; Real-Time Polymerase Chain Reaction |
顯示於: | 醫學院附設醫院 (臺大醫院) |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。