TSTA3 facilitates esophageal squamous cell carcinoma progression through regulating fucosylation of LAMP2 and ERBB2 Article Swipe
Ling Zhang
,
Yingzhen Gao
,
Xiaojuan Zhang
,
Min Guo
,
Jie Yang
,
Heyang Cui
,
Pengzhou Kong
,
Xia Niu
,
Yanghui Bi
,
Jing Xu
,
Ting Yan
,
Yanchun Ma
,
Jian Yang
,
Yu Qian
,
Fang Wang
,
Hongyi Li
,
Feng Liu
,
Xiaolong Cheng
,
Yongping Cui
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.7150/thno.48225
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.7150/thno.48225
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.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.7150/thno.48225
- OA Status
- gold
- Cited By
- 20
- References
- 57
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3089037986
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3089037986Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.7150/thno.48225Digital Object Identifier
- Title
-
TSTA3 facilitates esophageal squamous cell carcinoma progression through regulating fucosylation of LAMP2 and ERBB2Work title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-01-01Full publication date if available
- Authors
-
Ling Zhang, Yingzhen Gao, Xiaojuan Zhang, Min Guo, Jie Yang, Heyang Cui, Pengzhou Kong, Xia Niu, Yanghui Bi, Jing Xu, Ting Yan, Yanchun Ma, Jian Yang, Yu Qian, Fang Wang, Hongyi Li, Feng Liu, Xiaolong Cheng, Yongping CuiList of authors in order
- Landing page
-
https://doi.org/10.7150/thno.48225Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.7150/thno.48225Direct OA link when available
- Concepts
-
Fucosylation, Esophageal squamous cell carcinoma, Basal cell, Cancer research, Cell, Carcinoma, Chemistry, Medicine, Internal medicine, Glycoprotein, Biochemistry, GlycanTop concepts (fields/topics) attached by OpenAlex
- Cited by
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20Total citation count in OpenAlex
- Citations by year (recent)
-
2024: 2, 2023: 7, 2022: 9, 2021: 2Per-year citation counts (last 5 years)
- References (count)
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57Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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