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Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion
BACKGROUND: Helicobacter pylori infection is recognized as a major risk factor for gastric cancer (GC) progression; however, the underlying molecular mechanisms have remained to be fully elucidated. METHODS: qPCR and Western blot were used to detect mRNA level and relative protein expression. Wound...
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/PMC6613196/ https://www.ncbi.nlm.nih.gov/pubmed/31308697 http://dx.doi.org/10.2147/OTT.S201025 |
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author | Song, Yang Liu, Gao Liu, Shuang Chen, Rong Wang, Na Liu, Zhaoyu Zhang, Xiao Xiao, Zheng Liu, Lin |
author_facet | Song, Yang Liu, Gao Liu, Shuang Chen, Rong Wang, Na Liu, Zhaoyu Zhang, Xiao Xiao, Zheng Liu, Lin |
author_sort | Song, Yang |
collection | PubMed |
description | BACKGROUND: Helicobacter pylori infection is recognized as a major risk factor for gastric cancer (GC) progression; however, the underlying molecular mechanisms have remained to be fully elucidated. METHODS: qPCR and Western blot were used to detect mRNA level and relative protein expression. Wound healing assay and transwell were used to determine migration and invasion of cells. Calcium imaging was used to determine calcium signaling in cells. Luciferase reporter assay and immunohistochemistry were performed. RESULTS: In the present study, it was demonstrated that H. pylori infection in GC is closely associated with the depth of tumor invasion, lymph node metastasis, tumor-nodes-metastasis stage, and distant metastasis. Migration and invasion assays indicated that H. pylori infection enhanced the migration and invasion of GC cells in a Ca(2+)-dependent manner. Calcium imaging was applied to detect intracellular Ca(2+) and revealed that H. pylori induced an increase of intracellular Ca(2+) in GC cells through release from Ca(2+) stores and extracellular Ca(2+) influx. Further study indicated that H. pylori infection led to an upregulation of the expression of transient receptor potential cation channel subfamily C member 6 (TRPC6) and induced an increase of Ca(2+) through the TRPC6 channel. Furthermore, H. pylori increased TRPC6 transcription through the Wnt/β-catenin pathway, and Wnt/β-catenin/TRPC6 signaling was identified to be at least in part responsible for H. pylori-induced GC migration and invasion. Finally, it was observed that TRPC6 expression was significantly associated with the H. pylori infection status in GC tissues, and H. pylori infection was associated with metastasis and poor prognosis for GC patients. CONCLUSION: The present results indicate that H. pylori causes an upregulation of TRPC6 expression through the Wnt/β-catenin pathway to promote GC progression, and this interaction may serve as a promising target for GC therapy. |
format | Online Article Text |
id | pubmed-6613196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-66131962019-07-15 Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion Song, Yang Liu, Gao Liu, Shuang Chen, Rong Wang, Na Liu, Zhaoyu Zhang, Xiao Xiao, Zheng Liu, Lin Onco Targets Ther Original Research BACKGROUND: Helicobacter pylori infection is recognized as a major risk factor for gastric cancer (GC) progression; however, the underlying molecular mechanisms have remained to be fully elucidated. METHODS: qPCR and Western blot were used to detect mRNA level and relative protein expression. Wound healing assay and transwell were used to determine migration and invasion of cells. Calcium imaging was used to determine calcium signaling in cells. Luciferase reporter assay and immunohistochemistry were performed. RESULTS: In the present study, it was demonstrated that H. pylori infection in GC is closely associated with the depth of tumor invasion, lymph node metastasis, tumor-nodes-metastasis stage, and distant metastasis. Migration and invasion assays indicated that H. pylori infection enhanced the migration and invasion of GC cells in a Ca(2+)-dependent manner. Calcium imaging was applied to detect intracellular Ca(2+) and revealed that H. pylori induced an increase of intracellular Ca(2+) in GC cells through release from Ca(2+) stores and extracellular Ca(2+) influx. Further study indicated that H. pylori infection led to an upregulation of the expression of transient receptor potential cation channel subfamily C member 6 (TRPC6) and induced an increase of Ca(2+) through the TRPC6 channel. Furthermore, H. pylori increased TRPC6 transcription through the Wnt/β-catenin pathway, and Wnt/β-catenin/TRPC6 signaling was identified to be at least in part responsible for H. pylori-induced GC migration and invasion. Finally, it was observed that TRPC6 expression was significantly associated with the H. pylori infection status in GC tissues, and H. pylori infection was associated with metastasis and poor prognosis for GC patients. CONCLUSION: The present results indicate that H. pylori causes an upregulation of TRPC6 expression through the Wnt/β-catenin pathway to promote GC progression, and this interaction may serve as a promising target for GC therapy. Dove 2019-07-03 /pmc/articles/PMC6613196/ /pubmed/31308697 http://dx.doi.org/10.2147/OTT.S201025 Text en © 2019 Song 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 Song, Yang Liu, Gao Liu, Shuang Chen, Rong Wang, Na Liu, Zhaoyu Zhang, Xiao Xiao, Zheng Liu, Lin Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion |
title |
Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion |
title_full |
Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion |
title_fullStr |
Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion |
title_full_unstemmed |
Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion |
title_short |
Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion |
title_sort | helicobacter pylori upregulates trpc6 via wnt/β-catenin signaling to promote gastric cancer migration and invasion |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613196/ https://www.ncbi.nlm.nih.gov/pubmed/31308697 http://dx.doi.org/10.2147/OTT.S201025 |
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