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GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway
BACKGROUND: Gap junction beta-4 protein (GJB4), or connexin 30.3, a member of integral membrane proteins, has been shown to involve and may function as a tumor promoter in tumorigenesis. However, the role of GJB4 in gastric cancer (GC) is still unclear. MATERIALS AND METHODS: We used Progression-fre...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708386/ https://www.ncbi.nlm.nih.gov/pubmed/31692499 http://dx.doi.org/10.2147/OTT.S205601 |
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author | Liu, GuiYuan Pang, Yi Zhang, YaJun Fu, HaiRong Xiong, Wei Zhang, YongHui |
author_facet | Liu, GuiYuan Pang, Yi Zhang, YaJun Fu, HaiRong Xiong, Wei Zhang, YongHui |
author_sort | Liu, GuiYuan |
collection | PubMed |
description | BACKGROUND: Gap junction beta-4 protein (GJB4), or connexin 30.3, a member of integral membrane proteins, has been shown to involve and may function as a tumor promoter in tumorigenesis. However, the role of GJB4 in gastric cancer (GC) is still unclear. MATERIALS AND METHODS: We used Progression-free survival Kaplan-Meier analysis and Western blot analysis to detect the expression of GJB4 in GC tissues and cells. In addition, both in vitro and in vivo assays were used to determine the effect of GJB4 on malignant behavior in GC cells. RESULTS: We found that GJB4 was overexpressed in gastric cancer tissues and cells compared with normal tissues and cells. The high GJB4 expression was significantly associated with poor overall survival of GC patients. Knocking down GJB4 in GC cells significantly suppressed cell proliferation and migration. We found that the effects of GJB4-knockdown on GC cells were associated with downregulation of CTNNB1 and its downstream MYC, MMP7 and CCND1 expression. In addition, we found that the promotive effect of GJB4 overexpression on cell proliferation and migration was negated by XAV-939, which is the inhibitor of Wnt/CTNNB1 pathway. Therefore, we revealed a novel mechanism by which GJB4 could activate the Wnt/CTNNB1 pathway to promote GC cell’s proliferation and migration. CONCLUSION: This study offer insights into GJB4 function and indicate that GJB4 is a promising biomarker and therapeutic target for gastric cancer patients. |
format | Online Article Text |
id | pubmed-6708386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-67083862019-11-05 GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway Liu, GuiYuan Pang, Yi Zhang, YaJun Fu, HaiRong Xiong, Wei Zhang, YongHui Onco Targets Ther Original Research BACKGROUND: Gap junction beta-4 protein (GJB4), or connexin 30.3, a member of integral membrane proteins, has been shown to involve and may function as a tumor promoter in tumorigenesis. However, the role of GJB4 in gastric cancer (GC) is still unclear. MATERIALS AND METHODS: We used Progression-free survival Kaplan-Meier analysis and Western blot analysis to detect the expression of GJB4 in GC tissues and cells. In addition, both in vitro and in vivo assays were used to determine the effect of GJB4 on malignant behavior in GC cells. RESULTS: We found that GJB4 was overexpressed in gastric cancer tissues and cells compared with normal tissues and cells. The high GJB4 expression was significantly associated with poor overall survival of GC patients. Knocking down GJB4 in GC cells significantly suppressed cell proliferation and migration. We found that the effects of GJB4-knockdown on GC cells were associated with downregulation of CTNNB1 and its downstream MYC, MMP7 and CCND1 expression. In addition, we found that the promotive effect of GJB4 overexpression on cell proliferation and migration was negated by XAV-939, which is the inhibitor of Wnt/CTNNB1 pathway. Therefore, we revealed a novel mechanism by which GJB4 could activate the Wnt/CTNNB1 pathway to promote GC cell’s proliferation and migration. CONCLUSION: This study offer insights into GJB4 function and indicate that GJB4 is a promising biomarker and therapeutic target for gastric cancer patients. Dove 2019-08-20 /pmc/articles/PMC6708386/ /pubmed/31692499 http://dx.doi.org/10.2147/OTT.S205601 Text en © 2019 Liu et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Liu, GuiYuan Pang, Yi Zhang, YaJun Fu, HaiRong Xiong, Wei Zhang, YongHui GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway |
title | GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway |
title_full | GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway |
title_fullStr | GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway |
title_full_unstemmed | GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway |
title_short | GJB4 promotes gastric cancer cell proliferation and migration via Wnt/CTNNB1 pathway |
title_sort | gjb4 promotes gastric cancer cell proliferation and migration via wnt/ctnnb1 pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708386/ https://www.ncbi.nlm.nih.gov/pubmed/31692499 http://dx.doi.org/10.2147/OTT.S205601 |
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