| Title | TSTA3 facilitates esophageal squamous cell carcinoma progression through regulating fucosylation of LAMP2 and ERBB2 |
| Authors | Zhang, Ling Gao, Yingzhen Zhang, Xiaojuan Guo, Min Yang, Jie Cui, Heyang Kong, Pengzhou Niu, Xia Bi, Yanghui Xu, Jing Yan, Ting Ma, Yanchun Yang, Jian Qian, Yu Wang, Fang Li, Hongyi Liu, Feng Cheng, Xiaolong Cui, Yongping |
| Affiliation | Shanxi Med Univ, Dept Pathol, Taiyuan 030001, Shanxi, Peoples R China Shanxi Med Univ, Shanxi Key Lab Carcinogenesis & Translat Res Esop, Taiyuan 030001, Shanxi, Peoples R China Peking Univ, Shenzhen Peking Univ Hong Kong Univ Sci & Technol, Shenzhen Hosp, Dept Oncol Radiat Oncol,Canc Inst, Shenzhen 518035, Peoples R China Shanxi Med Univ, Hosp 2, Dept Gastroenterol, Taiyuan 030001, Shanxi, Peoples R China Shanxi Med Univ, Dept Forens, Taiyuan 030001, Shanxi, Peoples R China |
| Keywords | BIOMARKER DISCOVERY CORE FUCOSYLATION SERUM BIOMARKER CANCER-CELLS FX ENZYME EXPRESSION GLYCOSYLATION FUCOSE MICE IDENTIFICATION |
| Issue Date | 2020 |
| Publisher | THERANOSTICS |
| Abstract | Background: TSTA3 gene encodes an enzyme responsible for synthesis of GDP-L-fucose as the only donor in fucosylation. This study was designed to explore clinical value, function and underlying mechanism of TSTA3 in the development of esophageal squamous cell carcinoma (ESCC). Methods: Whole genomic sequencing data from 663 ESCC patients and RNA sequencing data from 155 ESCC patients were used to analyze the copy number variation and mRNA expression of TSTA3 respectively. Immunohistochemistry based or not based on the tissue microarrays was used to detect its protein expression. Transwell assay and in vivo metastasis assay were used to study the effect of TSTA3 on invasion and metastasis of ESCC. Immunofluorescence was used to analyze fucosylation level. N-glycoproteomics and proteomics analysis, Lens Culinaris Agglutinin (LCA) and Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, glycosyltransferase activity kit and rescue assay were used to explore the mechanism of TSTA3. Results: TSTA3 was frequently amplified and overexpressed in ESCC. TSTA3 amplification and protein overexpression were significantly associated with malignant progression and poor prognosis of ESCC patients. TSTA3 knockdown significantly suppressed ESCC cells invasion and tumor dissemination by decreasing fucosylation level. Conversely, exogenous overexpression of TSTA3 led to increased invasion and tumor metastasis in vitro and in vivo by increasing fucosylation level. Moreover, core fucosylated LAMP2 and terminal fucosylated ERBB2 might be mediators of TSTA3-induced pro-invasion in ESCC and had a synergistic effect on the process. Peracetylated 2-F-Fuc, a fucosyltransferase activity inhibitor, reduced TSTA3 expression and fucosylation modification of LAMP2 and ERBB2, thereby inhibiting ESCC cell invasion. Conclusion: Our results indicate that TSTA3 may be a driver of ESCC metastasis through regulating fucosylation of LAMP2 and ERBB2. Fucosylation inhibitor may have prospect to suppress ESCC metastasis by blocking aberrant fucosylation. |
| URI | http://hdl.handle.net/20.500.11897/592313 |
| ISSN | 1838-7640 |
| DOI | 10.7150/thno.48225 |
| Indexed | SCI(E) |
| Appears in Collections: | 深圳医院 |
