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Published in: BMC Cancer 1/2021

01-12-2021 | Metastasis | Research

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

Authors: Peng Zhang, Jian Xu, Hua Zhang, Xiao-Yu Liu

Published in: BMC Cancer | Issue 1/2021

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Abstract

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.
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Literature
3.
go back to reference van Kalsbeek RJ, van der Pal HJH, Hjorth L, Winther JF, Michel G, Haupt R, et al. The European multistakeholder PanCareFollowUp project: novel, person-centred survivorship care to improve care quality, effectiveness, cost-effectiveness and accessibility for cancer survivors and caregivers. Eur J Cancer. 2021;153:74–85. https://doi.org/10.1016/j.ejca.2021.05.030.CrossRefPubMed van Kalsbeek RJ, van der Pal HJH, Hjorth L, Winther JF, Michel G, Haupt R, et al. The European multistakeholder PanCareFollowUp project: novel, person-centred survivorship care to improve care quality, effectiveness, cost-effectiveness and accessibility for cancer survivors and caregivers. Eur J Cancer. 2021;153:74–85. https://​doi.​org/​10.​1016/​j.​ejca.​2021.​05.​030.CrossRefPubMed
4.
go back to reference Gallicchio L, Tonorezos E, de Moor JS, Elena J, Farrell M, Green P, et al. Evidence Gaps in Cancer Survivorship Care: A Report from the 2019 National Cancer Institute Cancer Survivorship Workshop. J Natl Cancer Inst. 2021;113(9):1136–42.CrossRefPubMedPubMedCentral Gallicchio L, Tonorezos E, de Moor JS, Elena J, Farrell M, Green P, et al. Evidence Gaps in Cancer Survivorship Care: A Report from the 2019 National Cancer Institute Cancer Survivorship Workshop. J Natl Cancer Inst. 2021;113(9):1136–42.CrossRefPubMedPubMedCentral
8.
go back to reference Tørring ML, Murchie P, Hamilton W, Vedsted P, Esteva M, Winget M, et al. Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11720 patients in five countries. Br J Cancer. 2017;177(6):888–97. https://doi.org/10.1038/bjc.2017.236.CrossRef Tørring ML, Murchie P, Hamilton W, Vedsted P, Esteva M, Winget M, et al. Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11720 patients in five countries. Br J Cancer. 2017;177(6):888–97. https://​doi.​org/​10.​1038/​bjc.​2017.​236.CrossRef
19.
go back to reference Liu X, Wang T, Wang Y, Chen Z, Hua D, Yao X, et al. Orai1 is critical for Notch-driven aggressiveness under hypoxic conditions in triple-negative breast cancers. Biochim Biophys Acta Mol Basis Dis. 2018;1864(4 Pt A):975–86.CrossRefPubMed Liu X, Wang T, Wang Y, Chen Z, Hua D, Yao X, et al. Orai1 is critical for Notch-driven aggressiveness under hypoxic conditions in triple-negative breast cancers. Biochim Biophys Acta Mol Basis Dis. 2018;1864(4 Pt A):975–86.CrossRefPubMed
27.
go back to reference Tsanou E, Peschos D, Batistatou A, Charalabopoulos A, Charalabopoulos K. The E-cadherin adhesion molecule and colorectal cancer. A global literature approach. Anticancer Res. 2008;28(6A):3815–26.PubMed Tsanou E, Peschos D, Batistatou A, Charalabopoulos A, Charalabopoulos K. The E-cadherin adhesion molecule and colorectal cancer. A global literature approach. Anticancer Res. 2008;28(6A):3815–26.PubMed
Metadata
Title
Identification of TRPV4 as a novel target in invasiveness of colorectal cancer
Authors
Peng Zhang
Jian Xu
Hua Zhang
Xiao-Yu Liu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08970-7

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