ArticleThe Journal of biological chemistry2016
Depletion of the Human Ion Channel TRPM2 in Neuroblastoma Demonstrates Its Key Role in Cell Survival through Modulation of Mitochondrial Reactive Oxygen Species and Bioenergetics.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 73 citations in OpenAlex.
- Pathophysiological significance of the TRPM2 ion channel as a potential target in cancer, neurological disorders, and ischemia/reperfusion injury.Pharmacological research · 2026Review
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.Frontiers in immunology · 2024Review
- TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches.Biomolecules · 2023Review
- Identification of TRPM2 as a prognostic factor correlated with immune infiltration in ovarian cancer.Journal of ovarian research · 2023Article
- TRPM2-mediated CaCell communication and signaling : CCS · 2023Review
- TRPM2: bridging calcium and ROS signaling pathways-implications for human diseases.Frontiers in physiology · 2023Review
- The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression.Scientific reports · 2022Article
- Amantadine Attenuated Hypoxia-Induced Mitochondrial Oxidative Neurotoxicity, Apoptosis, and Inflammation via the Inhibition of TRPM2 and TRPV4 Channels.Molecular neurobiology · 2022Article
- The human ion channel TRPM2 modulates cell survival in neuroblastoma through E2F1 and FOXM1.Scientific reports · 2022Article
- The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies.Acta pharmaceutica Sinica. B · 2022Review
- A novel antagonist of TRPM2 and TRPV4 channels: Carvacrol.Metabolic brain disease · 2022Article
- Ion Channel Involvement in Tumor Drug Resistance.Journal of personalized medicine · 2022Review
- On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications.Frontiers in oncology · 2022Review
- Article
- Curcumin Attenuates Hypoxia-Induced Oxidative Neurotoxicity, Apoptosis, Calcium, and Zinc Ion Influxes in a Neuronal Cell Line: Involvement of TRPM2 Channel.Neurotoxicity research · 2021Article
- Roles of NADMolecules (Basel, Switzerland) · 2020Review
- Mechanistic study of mtROS-JNK-SOD2 signaling in bupivacaine-induced neuron oxidative stress.Aging · 2020Article
- Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance.Cancers · 2020Review
- Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy.Cell death & disease · 2020Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Transient receptor potential melastatin 2 (TRPM2) ion channel has an essential function in modulating cell survival following oxidant injury and is highly expressed in many cancers including neuroblastoma. Here, in xenografts generated from neuroblastoma cells in which TRPM2 was depleted with CRISPR/Cas9 technology and in in vitro experiments, tumor growth was significantly inhibited and doxorubicin sensitivity increased. The hypoxia-inducible transcription factor 1/2α (HIF-1/2α) signaling cascade including proteins involved in oxidant stress, glycolysis, and mitochondrial function was suppressed by TRPM2 depletion. TRPM2-depleted SH-SY5Y neuroblastoma cells demonstrated reduced oxygen consumption and ATP production after doxorubicin, confirming impaired cellular bioenergetics. In cells in which TRPM2 was depleted, mitochondrial superoxide production was significantly increased, particularly following doxorubicin. Ectopic expression of superoxide dismutase 2 (SOD2) reduced ROS and preserved viability of TRPM2-depleted cells, however, failed to restore ATP levels. Mitochondrial reactive oxygen species (ROS) were also significantly increased in cells in which TRPM2 function was inhibited by TRPM2-S, and pretreatment of these cells with the antioxidant MitoTEMPO significantly reduced ROS levels in response to doxorubicin and protected cell viability. Expression of the TRPM2 pore mutant E960D, in which calcium entry through TRPM2 is abolished, also resulted in significantly increased mitochondrial ROS following doxorubicin treatment, showing the critical role of TRPM2-mediated calcium entry. These findings demonstrate the important function of TRPM2 in modulation of cell survival through mitochondrial ROS, and the potential of targeted inhibition of TRPM2 as a therapeutic approach to reduce cellular bioenergetics, tumor growth, and enhance susceptibility to chemotherapeutic agents.
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