Study the clinical significance of tryptophanyl-tRNA synthetase in oral cancer and reveal its role in cancer cell invasiveness
| Autor: | Chien Wei Lee, 李健瑋 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. Previously, we identified the angiostatic agent tryptophanyl-tRNA synthetase (TrpRS) as a dysregulated protein in OSCC based on a proteomics approach. Herein, we show that TrpRS is overexpressed in OSCC tissues (139/146, 95.2%) compared with adjacent normal tissues and that TrpRS expression positively correlates with tumor stage, overall TNM stage, perineural invasion and tumor depth. Importantly, the TrpRS levels were significantly higher in tumor cells from metastatic lymph nodes than in corresponding primary tumor cells. TrpRS knockdown or treatment with conditioned media obtained from TrpRS-knockdown cells significantly reduced oral cancer cell viability and invasiveness. TrpRS overexpression promoted cell migration and invasion. In addition, the extracellular addition of TrpRS rescued the invasion ability of TrpRS-knockdown cells. Subcellular fractionation and immunofluorescence staining demonstrated that TrpRS was distributed on the cell surface, suggesting that secreted TrpRS promotes OSCC progression via an extrinsic pathway. The SILAC-based quantitative proteomics analysis further revealed that TrpRS is involved in cell viability and adhesion through regulating the expressions of caspase7, Apaf-1, mitotic cohesion complex, PAI1, Trio, Rac1, ROCK, AKT, NFκB, PLAU and PLAUR. Furthermore, the TrpRS regulated OSCC cell invasiveness might through modulating extracellular MMP2 enzyme activity. Collectively, our results demonstrate the clinical significance and a novel role of TrpRS in OSCC. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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