ArticleProceedings of the National Academy of Sciences of the United States of America2020
Mechanoactivation of NOX2-generated ROS elicits persistent TRPM8 Ca
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Cell biomechanics on muscle atrophy: from intricate mechanisms to therapeutic frontiers.Annals of medicine · 2025Review
- Microtubule-Dependent CaJournal of the American Heart Association · 2025Article
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Biological physics to uncover cell signaling.Biophysical reviews · 2025Review
- Highly spatial-temporal electrochemical profiling of molecules trafficking at a single mitochondrion in one living cell.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Role of Oxidative Stress in the Occurrence, Development, and Treatment of Breast Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Differential Effects of Confinement-Induced ROS Accumulation on Highly Motile Cancerous and Non-Cancerous Cells.AIChE journal. American Institute of Chemical Engineers · 2024Article
- Hypertrophic cardiomyopathy-associated mutations drive stromal activation via EGFR-mediated paracrine signaling.Science advances · 2024Article
- Peripheral CCL2-CCR2 signalling contributes to chronic headache-related sensitization.Brain : a journal of neurology · 2023Article
- Prognostic value and immune infiltration of ARMC10 in pancreatic adenocarcinoma via integrated bioinformatics analyses.Heliyon · 2023Article
- TRPM8 promotes hepatocellular carcinoma progression by inducing SNORA55 mediated nuclear-mitochondrial communication.Cancer gene therapy · 2023Article
- Article
- Targeting M2 Macrophages with a Novel NADPH Oxidase Inhibitor.Antioxidants (Basel, Switzerland) · 2023Article
- Elevation of Cytoplasmic Calcium Suppresses Microtentacle Formation and Function in Breast Tumor Cells.Cancers · 2023Article
- Therapeutic potential of TRPM8 channels in cancer treatment.Frontiers in pharmacology · 2023Review
- The physiological sensor channels TRP and piezo: Nobel Prize in Physiology or Medicine 2021.Physiological reviews · 2022Article
- Cardiomyocyte Microtubules: Control of Mechanics, Transport, and Remodeling.Annual review of physiology · 2022Review
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Review
- Calcium signaling: breast cancer's approach to manipulation of cellular circuitry.Biophysical reviews · 2020Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Changes in the mechanical microenvironment and mechanical signals are observed during tumor progression, malignant transformation, and metastasis. In this context, understanding the molecular details of mechanotransduction signaling may provide unique therapeutic targets. Here, we report that normal breast epithelial cells are mechanically sensitive, responding to transient mechanical stimuli through a two-part calcium signaling mechanism. We observed an immediate, robust rise in intracellular calcium (within seconds) followed by a persistent extracellular calcium influx (up to 30 min). This persistent calcium was sustained via microtubule-dependent mechanoactivation of NADPH oxidase 2 (NOX2)-generated reactive oxygen species (ROS), which acted on transient receptor potential cation channel subfamily M member 8 (TRPM8) channels to prolong calcium signaling. In contrast, the introduction of a constitutively active oncogenic KRas mutation inhibited the magnitude of initial calcium signaling and severely blunted persistent calcium influx. The identification that oncogenic KRas suppresses mechanically-induced calcium at the level of ROS provides a mechanism for how KRas could alter cell responses to tumor microenvironment mechanics and may reveal chemotherapeutic targets for cancer. Moreover, we find that expression changes in both NOX2 and TRPM8 mRNA predict poor clinical outcome in estrogen receptor (ER)-negative breast cancer patients, a population with limited available treatment options. The clinical and mechanistic data demonstrating disruption of this mechanically-activated calcium pathway in breast cancer patients and by KRas activation reveal signaling alterations that could influence cancer cell responses to the tumor mechanical microenvironment and impact patient survival.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.