title: Overexpressed tryptophanyl-tRNA synthetase, an angiostatic protein, enhances oral cancer cell invasiveness.
abstract: 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 further revealed that TrpRS was distributed on the cell surface, suggesting that secreted TrpRS promotes OSCC progression via an extrinsic pathway. Collectively, our results demonstrated the clinical significance and a novel role of TrpRS in OSCC.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Lin-Kou, Tao-Yuan, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yan-Yu
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Lin-Kou, Tao-Yuan, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.|Pathology Core, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.|Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.|Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Yu
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection; D014369:Tryptophan-tRNA Ligase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014369:Tryptophan-tRNA Ligase
keywords: invasion; migration; oral squamous cell carcinoma; tryptophanyl-tRNA synthetase