Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells

Abstract The transient receptor potential ankyrin type 1 (TRPA1) channel belongs to the TRP superfamily of ion channels. TRPA1 is a membrane protein with multiple functions able to respond to noxious stimuli, reactive oxygen species, inflammatory cytokines or pungent substances, and it participates...

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Autores principales: Florentina Cojocaru, Tudor Şelescu, Dan Domocoş, Luminiţa Măruţescu, Gabriela Chiritoiu, Nicoleta-Raluca Chelaru, Simona Dima, Dan Mihăilescu, Alexandru Babes, Dana Cucu
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:4088ef873fe941ba9fc45e93f09021972021-12-02T15:23:28ZFunctional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells10.1038/s41598-021-81250-32045-2322https://doaj.org/article/4088ef873fe941ba9fc45e93f09021972021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81250-3https://doaj.org/toc/2045-2322Abstract The transient receptor potential ankyrin type 1 (TRPA1) channel belongs to the TRP superfamily of ion channels. TRPA1 is a membrane protein with multiple functions able to respond to noxious stimuli, reactive oxygen species, inflammatory cytokines or pungent substances, and it participates in pain signalling, taste, inflammation and various steps of the tumorigenic process. To date, no reports have addressed the expression and function of TRPA1 in pancreatic ductal adenocarcinoma (PDAC) cells. This work reports the endogenous expression of TRPA1 channels in human pancreatic adenocarcinoma cell lines and provides insights into the function of the TRPA1 protein in the Panc-1 cell line. This study reports that cell lines isolated from PDAC patients had different levels of TRPA1 expression. The channel activity in Panc-1 cells, as assessed with electrophysiological (whole-cell patch clamp) and microfluorimetry methods, showed that non-selective cationic currents were activated by allyl isothiocyanate (AITC) in Panc-1 cells and inhibited by the selective TRPA1 antagonist A-967079. The current elicited by the specific agonist was associated with a robust increase in intracellular Ca2+. Furthermore, siRNA-induced downregulation of TRPA1 enhanced cell migration in the wound healing assay, indicating a possible role of ion channels independent from pore function. Finally, TRPA1 activation changed the cell cycle progression. Taken together, these results support the idea of channel-dependent and independent role for TRPA1 in tumoral processes.Florentina CojocaruTudor ŞelescuDan DomocoşLuminiţa MăruţescuGabriela ChiritoiuNicoleta-Raluca ChelaruSimona DimaDan MihăilescuAlexandru BabesDana CucuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Florentina Cojocaru
Tudor Şelescu
Dan Domocoş
Luminiţa Măruţescu
Gabriela Chiritoiu
Nicoleta-Raluca Chelaru
Simona Dima
Dan Mihăilescu
Alexandru Babes
Dana Cucu
Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells
description Abstract The transient receptor potential ankyrin type 1 (TRPA1) channel belongs to the TRP superfamily of ion channels. TRPA1 is a membrane protein with multiple functions able to respond to noxious stimuli, reactive oxygen species, inflammatory cytokines or pungent substances, and it participates in pain signalling, taste, inflammation and various steps of the tumorigenic process. To date, no reports have addressed the expression and function of TRPA1 in pancreatic ductal adenocarcinoma (PDAC) cells. This work reports the endogenous expression of TRPA1 channels in human pancreatic adenocarcinoma cell lines and provides insights into the function of the TRPA1 protein in the Panc-1 cell line. This study reports that cell lines isolated from PDAC patients had different levels of TRPA1 expression. The channel activity in Panc-1 cells, as assessed with electrophysiological (whole-cell patch clamp) and microfluorimetry methods, showed that non-selective cationic currents were activated by allyl isothiocyanate (AITC) in Panc-1 cells and inhibited by the selective TRPA1 antagonist A-967079. The current elicited by the specific agonist was associated with a robust increase in intracellular Ca2+. Furthermore, siRNA-induced downregulation of TRPA1 enhanced cell migration in the wound healing assay, indicating a possible role of ion channels independent from pore function. Finally, TRPA1 activation changed the cell cycle progression. Taken together, these results support the idea of channel-dependent and independent role for TRPA1 in tumoral processes.
format article
author Florentina Cojocaru
Tudor Şelescu
Dan Domocoş
Luminiţa Măruţescu
Gabriela Chiritoiu
Nicoleta-Raluca Chelaru
Simona Dima
Dan Mihăilescu
Alexandru Babes
Dana Cucu
author_facet Florentina Cojocaru
Tudor Şelescu
Dan Domocoş
Luminiţa Măruţescu
Gabriela Chiritoiu
Nicoleta-Raluca Chelaru
Simona Dima
Dan Mihăilescu
Alexandru Babes
Dana Cucu
author_sort Florentina Cojocaru
title Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells
title_short Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells
title_full Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells
title_fullStr Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells
title_full_unstemmed Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells
title_sort functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/4088ef873fe941ba9fc45e93f0902197
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