https://scholars.lib.ntu.edu.tw/handle/123456789/569175
標題: | HDAC2 promotes cell migration/invasion abilities through HIF-1α stabilization in human oral squamous cell carcinoma | 作者: | Chang C.-C. BEEN-REN LIN Chen S.-T. Hsieh T.-H. Li Y.-J. YEN-PING KUO |
公開日期: | 2011 | 卷: | 40 | 期: | 7 | 起(迄)頁: | 567-575 | 來源出版物: | Journal of Oral Pathology and Medicine | 摘要: | Background: Histone deacetylase 2 (HDAC2) expressions in oral squamous cell carcinoma (OSCC) had been implicated in advanced stage and poor prognosis. It suggests a possible link between the migration/invasion potential of oral cancer cells and the prevalent expression of HDAC2. Methods: Five head and neck cancer (HNC) cell lines, including Ca9-22, Cal-27, HSC-3, SAS, and TW2.6, were used. Cells stably overexpressing HDAC2 and shRNA against HDAC2 were established to investigate migration/invasion ability in vitro and tumorigenesis and progression in vivo. Results: We found that alterations in the HDAC2 level in OSCC cell lines modulated their invasive ability with a positive correlation. Animal model also showed that knockdown of HDAC2 expression in SAS cells, originally containing high endogenous HDAC2 expression, resulted in decrease in tumor initiation and progression. Using high-throughput transcriptome analysis, numerous genes involved in HIF-1α-associated pathways were found. At the mechanism levels, using agents to block de novo protein synthesis or prevent protein degradation by ubiquitination, we found the stability of hypoxia inducible factor 1α (HIF-1α) protein was maintained in OSCC cells with HDAC2 overexpression. In addition, co-immunoprecipitation assay also revealed that HDAC2-mediated HIF-1α protein stability is because of direct interaction of HIF-1α with von Hippel-Lindau (VHL) protein. Conclusions: Our work demonstrates that HDAC2 maintains HIF-1α stability, probably at the level of protein modification, which in turn leads to the increase in cell invasion/migration ability in oral cancer progression. These findings implicate the potential of HDAC inhibitors for oral cancer therapy. ? 2011 John Wiley & Sons A/S. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-79960629010&doi=10.1111%2fj.1600-0714.2011.01009.x&partnerID=40&md5=c8b657f3e8e507918cfb8fdf3d62c24a https://scholars.lib.ntu.edu.tw/handle/123456789/569175 |
ISSN: | 0904-2512 | DOI: | 10.1111/j.1600-0714.2011.01009.x | SDG/關鍵字: | histone deacetylase 2; hypoxia inducible factor 1alpha; short hairpin RNA; transcriptome; von Hippel Lindau protein; animal cell; animal experiment; animal model; article; cancer growth; carcinoma cell; cell invasion; cell migration; clinical article; concentration (parameters); controlled study; correlational study; female; gene overexpression; gene silencing; human; human cell; immunoprecipitation; molecular mechanics; mouse; mouth carcinoma; nonhuman; priority journal; protein degradation; protein modification; protein protein interaction; protein stability; protein synthesis; squamous cell carcinoma; stable expression; ubiquitination; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Disease Progression; Female; Gene Expression Profiling; Gene Knockdown Techniques; Histone Deacetylase 2; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lymphatic Metastasis; Lysine; Mice; Mice, SCID; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Transplantation; Protein Processing, Post-Translational; Protein Stability; Random Allocation; Ubiquitination; Von Hippel-Lindau Tumor Suppressor Protein |
顯示於: | 牙醫學系 |
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