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A novel YAP1/SLC35B4 regulatory axis contributes to proliferation and progression of gastric carcinoma

Solute carrier family 35 member B4 (SLC35B4), a nucleotide sugar transporter, is capable of transporting UDP-xylose and UDP-GlcNAc from the cytoplasm to the lumen of the endoplasmic reticulum and Golgi. SLC35B4 has a pivotal role in glycosylation of biological macromolecules. However, its functional...

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Autores principales: Liu, Jun, Zhao, Xinhui, Wang, Ke, Zhang, Xiang, Yu, Yanping, Lv, Yongzhi, Zhang, Shun, Zhang, Long, Guo, Yuan, Li, Yunlong, Yang, Angang, Zhang, Rui, Li, Jipeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555804/
https://www.ncbi.nlm.nih.gov/pubmed/31175271
http://dx.doi.org/10.1038/s41419-019-1674-2
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author Liu, Jun
Zhao, Xinhui
Wang, Ke
Zhang, Xiang
Yu, Yanping
Lv, Yongzhi
Zhang, Shun
Zhang, Long
Guo, Yuan
Li, Yunlong
Yang, Angang
Zhang, Rui
Li, Jipeng
author_facet Liu, Jun
Zhao, Xinhui
Wang, Ke
Zhang, Xiang
Yu, Yanping
Lv, Yongzhi
Zhang, Shun
Zhang, Long
Guo, Yuan
Li, Yunlong
Yang, Angang
Zhang, Rui
Li, Jipeng
author_sort Liu, Jun
collection PubMed
description Solute carrier family 35 member B4 (SLC35B4), a nucleotide sugar transporter, is capable of transporting UDP-xylose and UDP-GlcNAc from the cytoplasm to the lumen of the endoplasmic reticulum and Golgi. SLC35B4 has a pivotal role in glycosylation of biological macromolecules. However, its functional roles and regulatory mechanisms in malignant diseases remain unknown. Here, using the cDNA arrays, promoter reporter assays, and chromatin immunoprecipitation assays, we demonstrated that SLC35B4 is directly transactivated by YAP1–TEADs complex in gastric cancer (GC) cells. CCK-8, plate colony formation and soft agar assays revealed that SLC35B4 is essential for survival and proliferation in GC cells and nude mice models. SLC35B4 expression is markedly higher in GC tissues compared with control noncancerous tissues. Immunohistochemistry revealed that SLC35B4 expression is positively correlated with YAP1 expression in human GC tissues, and this correlation is also confirmed in the GC TCGA data set. GC patients with high levels of SLC35B4 expression have poorer prognosis than those with low levels of SLC35B4 expression. Collectively, our findings defined SLC35B4 as an important downstream oncogenic target of YAP1, suggesting that dysregulated signaling of a novel YAP1/SLC35B4 axis promotes GC development and progression, and this axis could be a potential candidate for prognosis and therapeutics in GC.
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spelling pubmed-65558042019-06-21 A novel YAP1/SLC35B4 regulatory axis contributes to proliferation and progression of gastric carcinoma Liu, Jun Zhao, Xinhui Wang, Ke Zhang, Xiang Yu, Yanping Lv, Yongzhi Zhang, Shun Zhang, Long Guo, Yuan Li, Yunlong Yang, Angang Zhang, Rui Li, Jipeng Cell Death Dis Article Solute carrier family 35 member B4 (SLC35B4), a nucleotide sugar transporter, is capable of transporting UDP-xylose and UDP-GlcNAc from the cytoplasm to the lumen of the endoplasmic reticulum and Golgi. SLC35B4 has a pivotal role in glycosylation of biological macromolecules. However, its functional roles and regulatory mechanisms in malignant diseases remain unknown. Here, using the cDNA arrays, promoter reporter assays, and chromatin immunoprecipitation assays, we demonstrated that SLC35B4 is directly transactivated by YAP1–TEADs complex in gastric cancer (GC) cells. CCK-8, plate colony formation and soft agar assays revealed that SLC35B4 is essential for survival and proliferation in GC cells and nude mice models. SLC35B4 expression is markedly higher in GC tissues compared with control noncancerous tissues. Immunohistochemistry revealed that SLC35B4 expression is positively correlated with YAP1 expression in human GC tissues, and this correlation is also confirmed in the GC TCGA data set. GC patients with high levels of SLC35B4 expression have poorer prognosis than those with low levels of SLC35B4 expression. Collectively, our findings defined SLC35B4 as an important downstream oncogenic target of YAP1, suggesting that dysregulated signaling of a novel YAP1/SLC35B4 axis promotes GC development and progression, and this axis could be a potential candidate for prognosis and therapeutics in GC. Nature Publishing Group UK 2019-06-07 /pmc/articles/PMC6555804/ /pubmed/31175271 http://dx.doi.org/10.1038/s41419-019-1674-2 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Jun
Zhao, Xinhui
Wang, Ke
Zhang, Xiang
Yu, Yanping
Lv, Yongzhi
Zhang, Shun
Zhang, Long
Guo, Yuan
Li, Yunlong
Yang, Angang
Zhang, Rui
Li, Jipeng
A novel YAP1/SLC35B4 regulatory axis contributes to proliferation and progression of gastric carcinoma
title A novel YAP1/SLC35B4 regulatory axis contributes to proliferation and progression of gastric carcinoma
title_full A novel YAP1/SLC35B4 regulatory axis contributes to proliferation and progression of gastric carcinoma
title_fullStr A novel YAP1/SLC35B4 regulatory axis contributes to proliferation and progression of gastric carcinoma
title_full_unstemmed A novel YAP1/SLC35B4 regulatory axis contributes to proliferation and progression of gastric carcinoma
title_short A novel YAP1/SLC35B4 regulatory axis contributes to proliferation and progression of gastric carcinoma
title_sort novel yap1/slc35b4 regulatory axis contributes to proliferation and progression of gastric carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555804/
https://www.ncbi.nlm.nih.gov/pubmed/31175271
http://dx.doi.org/10.1038/s41419-019-1674-2
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