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Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway
Transmembrane protein 268 (TMEM268) encodes a novel human protein of previously unknown function. This study analyzed the biological activities and molecular mechanisms of TMEM268 in vivo and in vitro. We found that TMEM268 deletion decreases cell viability, proliferation, and cell adhesion as well...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748091/ https://www.ncbi.nlm.nih.gov/pubmed/30361615 http://dx.doi.org/10.1038/s41418-018-0223-3 |
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author | Hong, Dubeiqi Zhang, Xuan Li, Riyong Yu, Jiahong Lou, Yaxin He, Qihua Li, Xuanze Xu, Dong Lv, Ping Lin, Jian Chen, Yingyu |
author_facet | Hong, Dubeiqi Zhang, Xuan Li, Riyong Yu, Jiahong Lou, Yaxin He, Qihua Li, Xuanze Xu, Dong Lv, Ping Lin, Jian Chen, Yingyu |
author_sort | Hong, Dubeiqi |
collection | PubMed |
description | Transmembrane protein 268 (TMEM268) encodes a novel human protein of previously unknown function. This study analyzed the biological activities and molecular mechanisms of TMEM268 in vivo and in vitro. We found that TMEM268 deletion decreases cell viability, proliferation, and cell adhesion as well as causing S-phase cell cycle arrest and disrupts cytoskeleton remolding. Xenograft tumor mouse model studies showed that TMEM268 deletion inhibits the tumorigenesis of BGC823 gastric cancer cells. In addition, TMEM268-deleted BGC823 cells failed to colonize the lungs after intravenous injection and to form metastatic engraftment in the peritoneum. Molecular mechanism studies showed a C-terminal interaction between TMEM268 and integrin subunit β4 (ITGB4). TMEM268 knockout promotes ITGB4 ubiquitin-mediated degradation, increasing the instability of ITGB4 and filamin A (FLNA). The reduced ITGB4 protein levels result in the disassociation of the ITGB4/PLEC complex and cytoskeleton remodeling. This study for the first time demonstrates that TMEM268 plays a positive role in the regulation of ITGB4 homeostasis. The above results may provide a new perspective that targeting the TMEM268/ITGB4 signaling axis for the treatment of gastric cancer, which deserves further investigation in the future. |
format | Online Article Text |
id | pubmed-6748091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67480912019-09-18 Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway Hong, Dubeiqi Zhang, Xuan Li, Riyong Yu, Jiahong Lou, Yaxin He, Qihua Li, Xuanze Xu, Dong Lv, Ping Lin, Jian Chen, Yingyu Cell Death Differ Article Transmembrane protein 268 (TMEM268) encodes a novel human protein of previously unknown function. This study analyzed the biological activities and molecular mechanisms of TMEM268 in vivo and in vitro. We found that TMEM268 deletion decreases cell viability, proliferation, and cell adhesion as well as causing S-phase cell cycle arrest and disrupts cytoskeleton remolding. Xenograft tumor mouse model studies showed that TMEM268 deletion inhibits the tumorigenesis of BGC823 gastric cancer cells. In addition, TMEM268-deleted BGC823 cells failed to colonize the lungs after intravenous injection and to form metastatic engraftment in the peritoneum. Molecular mechanism studies showed a C-terminal interaction between TMEM268 and integrin subunit β4 (ITGB4). TMEM268 knockout promotes ITGB4 ubiquitin-mediated degradation, increasing the instability of ITGB4 and filamin A (FLNA). The reduced ITGB4 protein levels result in the disassociation of the ITGB4/PLEC complex and cytoskeleton remodeling. This study for the first time demonstrates that TMEM268 plays a positive role in the regulation of ITGB4 homeostasis. The above results may provide a new perspective that targeting the TMEM268/ITGB4 signaling axis for the treatment of gastric cancer, which deserves further investigation in the future. Nature Publishing Group UK 2018-10-25 2019-08 /pmc/articles/PMC6748091/ /pubmed/30361615 http://dx.doi.org/10.1038/s41418-018-0223-3 Text en © The Author(s) 2018 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 Hong, Dubeiqi Zhang, Xuan Li, Riyong Yu, Jiahong Lou, Yaxin He, Qihua Li, Xuanze Xu, Dong Lv, Ping Lin, Jian Chen, Yingyu Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway |
title | Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway |
title_full | Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway |
title_fullStr | Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway |
title_full_unstemmed | Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway |
title_short | Deletion of TMEM268 inhibits growth of gastric cancer cells by downregulating the ITGB4 signaling pathway |
title_sort | deletion of tmem268 inhibits growth of gastric cancer cells by downregulating the itgb4 signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748091/ https://www.ncbi.nlm.nih.gov/pubmed/30361615 http://dx.doi.org/10.1038/s41418-018-0223-3 |
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