Title page for etd-0708118-093546


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URN etd-0708118-093546
Author Tzu-Wen Lin
Author's Email Address No Public.
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Department Institute of Biomedical Sciences
Year 2017
Semester 2
Degree Master
Type of Document
Language English
Title Investigation of hepatoma-derived growth factor (HDGF) membrane binding protein and biological functions in HDGF S103A mutation
Date of Defense 2018-07-13
Page Count 70
Keyword
  • Annexin A2 (ANXA2)
  • GRP78
  • Nucleophosmin (B23)
  • Nucleolin (NCL)
  • Hepatoma-derived growth factor (HDGF)
  • Hepatocellular carcinoma (HCC)
  • Abstract Hepatoma-derived growth factor (HDGF) is a nuclear targeted growth factor identified from human hepatocellular carcinoma (HCC) cell line, Huh7. Based on clinical studies, HDGF overexpression promotes tumor progression through stimulating proliferation and epithelial-mesenchymal transition (EMT). HDGF was considered as a poor prognostic factor for cancer patients in survival, however, the signaling pathway of HDGF is remains unclear. Our recent study indicates that HDGF may exerts its oncogenic function via binding to membrane Nucleolin (NCL) and activating the downstream PI3K/AKT signaling. HDGF is consist of PWWP and C140 domains; NCL is composed of three distinct domains (domain I, II, III). By using Alexa-488 fluorescent labeled HDGF, we have determined that the exogenous HDGF could be uptake within 4 hours. Subsequently, by using solid phase binding assay, we have demonstrated that HDGF bound to NCL domain II via its PWWP domain. By using affinity chromatography and MASS spectrum, we have characterized several membrane proteins such as B23, Annexin A2 and GRP78 that involved in HDGF-binding membrane complex. Using antibodies neutralization, we have confirmed not only NCL, but also B23 and GRP78 that play important roles in HDGF interaction and HDGF uptake. Furthermore, previous studies showed that S103 phosphorylation site playing a critical role in regulating HDGF mitogenic function. Our data has suggested HDGF S103A mutation lead to loss of HDGF-mediated cell invasion and cell proliferation. This study has revealed the importance of NCL domain II in HDGF binding; Besides, S103 position in HDGF is critical for the biological function in HDGF. This finding suggested that targeting HDGF membrane bound may provide a new strategy for cancer therapy and HDGF related diseases.
    Advisory Committee
  • Chyuan Sheu - chair
  • Chun-Lin Chen - co-chair
  • Ming Hong Tai - advisor
  • Files
  • etd-0708118-093546.pdf
  • Indicate in-campus at 99 year and off-campus access at 99 year.
    Date of Submission 2018-08-08

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