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Identification of TRPV4 as a novel target in invasiveness of colorectal cancer

BACKGROUND: Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown. METHODS: Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical...

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Autores principales: Zhang, Peng, Xu, Jian, Zhang, Hua, Liu, Xiao-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611894/
https://www.ncbi.nlm.nih.gov/pubmed/34814869
http://dx.doi.org/10.1186/s12885-021-08970-7
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author Zhang, Peng
Xu, Jian
Zhang, Hua
Liu, Xiao-Yu
author_facet Zhang, Peng
Xu, Jian
Zhang, Hua
Liu, Xiao-Yu
author_sort Zhang, Peng
collection PubMed
description BACKGROUND: Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown. METHODS: Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1. RESULTS: Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1. CONCLUSIONS: Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08970-7.
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spelling pubmed-86118942021-11-29 Identification of TRPV4 as a novel target in invasiveness of colorectal cancer Zhang, Peng Xu, Jian Zhang, Hua Liu, Xiao-Yu BMC Cancer Research BACKGROUND: Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown. METHODS: Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1. RESULTS: Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1. CONCLUSIONS: Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08970-7. BioMed Central 2021-11-23 /pmc/articles/PMC8611894/ /pubmed/34814869 http://dx.doi.org/10.1186/s12885-021-08970-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhang, Peng
Xu, Jian
Zhang, Hua
Liu, Xiao-Yu
Identification of TRPV4 as a novel target in invasiveness of colorectal cancer
title Identification of TRPV4 as a novel target in invasiveness of colorectal cancer
title_full Identification of TRPV4 as a novel target in invasiveness of colorectal cancer
title_fullStr Identification of TRPV4 as a novel target in invasiveness of colorectal cancer
title_full_unstemmed Identification of TRPV4 as a novel target in invasiveness of colorectal cancer
title_short Identification of TRPV4 as a novel target in invasiveness of colorectal cancer
title_sort identification of trpv4 as a novel target in invasiveness of colorectal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611894/
https://www.ncbi.nlm.nih.gov/pubmed/34814869
http://dx.doi.org/10.1186/s12885-021-08970-7
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