博士 / 國防醫學院 / 生命科學研究所 / 105 / Metabolic reprograming and Warburg effect as an important issue in head and neck squamous cell carcinoma (HNSCC) involved drug-resistance, tumorigenesis and tumor metastasis. Solute Carrie family 2, also called glucose transporter family members play an initial role in glycolysis pathway by controlling transporter efficiency. However, detail mechanism of GLUT family in HNSCC tumorigenesis has not been fully investigated. In our study, GLUT4 had most significant value compared with other family members associating with HNSCC patients’ survival rate. Furthermore, we found the GLUT4 protein level positive correlated with N status by immunohistochemistry analysis. The results showed that increased GLUT4 expression level was associated with poor overall survival (OS, P=0.035) and recurrence-free survival (RFS, P=0.001). We further confirmed that GLUT4 could promote HNSCC migration and invasion in vitro and in vivo through two-way complementary model including GLUT4 overexpression or knockdown stable cell models. We established microarray chips to investigate the detail molecular mechanism. Ingenuity Pathway Analysis (IPA) software dissected tripartite motif-containing 24 (TRIM24) transcription factor as the top ranking downstream regulator of GLUT4. DDX58 was further validated that the major downstream target of GLUT4-TRIM24 axis in HNSCC. Knockdown of DDX58 could reverse the phenotype included migration and invasion by GLUT4-TRIM24 activation in our model. Combined all evidence, GLUT4/TRIM24/DDX58 could be an independent prognostic marker for HNSCC patients. These findings may a novel therapeutic development to combat metastasis of HNSCC in the future.
| Identifer | oai:union.ndltd.org:TW/105NDMC0105026 |
| Date | January 2017 |
| Creators | CHANG, YU-CHAN, 張御展 |
| Contributors | Hsiao, Michael, 蕭宏昇 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 117 |
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