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

Florentina Cojocaru,Nicoleta-Raluca Chelaru,Luminiţa Măruţescu,Tudor Şelescu,Simona Dima,Dan Domocoş,Dana Cucu,Dan Mihăilescu,Gabriela Chiritoiu,Alexandru Babes

doi:10.1038/s41598-021-81250-3

Florentina Cojocaru, Nicoleta-Raluca Chelaru + Show 8 more

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https://doi.org/10.1038/s41598-021-81250-3

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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.

Highlights

The transient receptor potential ankyrin type 1 (TRPA1) channel belongs to the TRP superfamily of ion channels
Numerous recent reports describe the involvement of TRP channels in the migration or proliferation of cancer cells, and the results are conflicting depending on the tumour type studied, they support the putative role of TRP channels as therapeutic targets for cancer
Other reports insist on the role of some TRP proteins in the signalling pathways, through pore -independent contribution to the tumorigenic p rocess[12]

Summary

Introduction

The transient receptor potential ankyrin type 1 (TRPA1) channel belongs to the TRP superfamily of ion channels. Transient receptor potential ankyrin type 1 (TRPA1), the only member of the ankyrin subfamily, has high Ca2+ permeability and is activated by various stimuli, such as cold temperatures, pungent compounds, reactive oxygen species and endogenous compounds[8] This channel is overexpressed in some cancer types but has largely been overlooked by previous studies. We focused on the conducting roles of TRPA1 in the migration and cell cycle of PDAC cells as well as on the putative endogenous expression and activation of these channels The results of this new study on TRPA1 expression in pancreatic adenocarcinoma cell lines provide insights into the function of TRPA1 channels in cancer and their putative role as participants to the cancerogenic process via channel-independent mechanisms. Expression of TRPA1 channels in PDAC cell lines Previous studies reported that TRPA1 is detectable in glioblastoma, breast cancer and other various cancer

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