Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells

Moderate levels of reactive oxygen species (ROS), such as hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), fuel tumor metastasis and invasion in a variety of cancer types. Conversely, excessive ROS levels can impair tumor growth and metastasis by triggering cancer cell death....

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Main Authors: Francesco Moccia, Daniela Montagna
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/9/1261
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author Francesco Moccia
Daniela Montagna
author_facet Francesco Moccia
Daniela Montagna
author_sort Francesco Moccia
collection DOAJ
description Moderate levels of reactive oxygen species (ROS), such as hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), fuel tumor metastasis and invasion in a variety of cancer types. Conversely, excessive ROS levels can impair tumor growth and metastasis by triggering cancer cell death. In order to cope with the oxidative stress imposed by the tumor microenvironment, malignant cells exploit a sophisticated network of antioxidant defense mechanisms. Targeting the antioxidant capacity of cancer cells or enhancing their sensitivity to ROS-dependent cell death represent a promising strategy for alternative anticancer treatments. Transient Receptor Potential Ankyrin 1 (TRPA1) is a redox-sensitive non-selective cation channel that mediates extracellular Ca<sup>2+</sup> entry upon an increase in intracellular ROS levels. The ensuing increase in intracellular Ca<sup>2+</sup> concentration can in turn engage a non-canonical antioxidant defense program or induce mitochondrial Ca<sup>2+</sup> dysfunction and apoptotic cell death depending on the cancer type. Herein, we sought to describe the opposing effects of ROS-dependent TRPA1 activation on cancer cell fate and propose the pharmacological manipulation of TRPA1 as an alternative therapeutic strategy to enhance cancer cell sensitivity to oxidative stress.
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spelling doaj.art-2e6385f4eeae48799a86152a9717789c2023-11-17T22:43:30ZengMDPI AGCells2073-44092023-04-01129126110.3390/cells12091261Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer CellsFrancesco Moccia0Daniela Montagna1Laboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, ItalyDepartment of Sciences Clinic-Surgical, Diagnostic and Pediatric, University of Pavia, 27100 Pavia, ItalyModerate levels of reactive oxygen species (ROS), such as hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), fuel tumor metastasis and invasion in a variety of cancer types. Conversely, excessive ROS levels can impair tumor growth and metastasis by triggering cancer cell death. In order to cope with the oxidative stress imposed by the tumor microenvironment, malignant cells exploit a sophisticated network of antioxidant defense mechanisms. Targeting the antioxidant capacity of cancer cells or enhancing their sensitivity to ROS-dependent cell death represent a promising strategy for alternative anticancer treatments. Transient Receptor Potential Ankyrin 1 (TRPA1) is a redox-sensitive non-selective cation channel that mediates extracellular Ca<sup>2+</sup> entry upon an increase in intracellular ROS levels. The ensuing increase in intracellular Ca<sup>2+</sup> concentration can in turn engage a non-canonical antioxidant defense program or induce mitochondrial Ca<sup>2+</sup> dysfunction and apoptotic cell death depending on the cancer type. Herein, we sought to describe the opposing effects of ROS-dependent TRPA1 activation on cancer cell fate and propose the pharmacological manipulation of TRPA1 as an alternative therapeutic strategy to enhance cancer cell sensitivity to oxidative stress.https://www.mdpi.com/2073-4409/12/9/1261cancerreactive oxygen specieshydrogen peroxideTransient Receptor Potential Ankyrin 1Ca<sup>2+</sup> signalingnuclear factor erythroid 2-related factor 2
spellingShingle Francesco Moccia
Daniela Montagna
Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells
Cells
cancer
reactive oxygen species
hydrogen peroxide
Transient Receptor Potential Ankyrin 1
Ca<sup>2+</sup> signaling
nuclear factor erythroid 2-related factor 2
title Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells
title_full Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells
title_fullStr Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells
title_full_unstemmed Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells
title_short Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells
title_sort transient receptor potential ankyrin 1 trpa1 channel as a sensor of oxidative stress in cancer cells
topic cancer
reactive oxygen species
hydrogen peroxide
Transient Receptor Potential Ankyrin 1
Ca<sup>2+</sup> signaling
nuclear factor erythroid 2-related factor 2
url https://www.mdpi.com/2073-4409/12/9/1261
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AT danielamontagna transientreceptorpotentialankyrin1trpa1channelasasensorofoxidativestressincancercells