ArticleAmerican journal of physiology. Cell physiology2018
The human ion channel TRPM2 modulates neuroblastoma cell survival and mitochondrial function through Pyk2, CREB, and MCU activation.
Article in American journal of physiology. Cell physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 56 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
- Zerumbet Ginger Extract Attenuates Chemotherapy-Induced Toxicity and Promotes Tumor Suppression in a Murine Breast Cancer Model.Food science & nutrition · 2025Article
- CREB5 promotes nodal metastasis of cervical cancer by regulation of APLN-induced lymphangiogenesis.Cell death discovery · 2025Article
- TRPM2: a pivotal player in tumor progression and a promising therapeutic target.Cancer cell international · 2025Review
- Crosstalk between calcium and reactive oxygen species signaling in cancer revisited.Cell calcium · 2025Review
- Novel Compounds Target Aberrant Calcium Signaling in the Treatment of Relapsed High-Risk Neuroblastoma.International journal of molecular sciences · 2025Article
- Transient receptor potential channels in dental inflammation and pain perception: A comprehensive review.Heliyon · 2025Article
- Roles of TRPM channels in glioma.Cancer biology & therapy · 2024Review
- Mitochondrial translation failure represses cholesterol gene expression via Pyk2-Gsk3β-Srebp2 axis.Life science alliance · 2024Article
- Advances in the role of ion channels in leukemia.Heliyon · 2024Review
- The TRPM2 ion channel regulates metabolic and thermogenic adaptations in adipose tissue of cold-exposed mice.Frontiers in endocrinology · 2024Article
- 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
- TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2023Review
- TRPM2 Channels: A Potential Therapeutic Target in Melanoma?International journal of molecular sciences · 2023Review
- MCU Upregulation Overactivates Mitophagy by Promoting VDAC1 Dimerization and Ubiquitination in the Hepatotoxicity of Cadmium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- TRPM2: bridging calcium and ROS signaling pathways-implications for human diseases.Frontiers in physiology · 2023Review
- TRPM2 protects against cisplatin-induced acute kidney injury and mitochondrial dysfunction via modulating autophagy.Theranostics · 2023Article
- Activated PyK2 and Its Associated Molecules Transduce Cellular Signaling from the Cancerous Milieu for Cancer Metastasis.International journal of molecular sciences · 2022Review
- The human ion channel TRPM2 modulates migration and invasion in neuroblastoma through regulation of integrin expression.Scientific reports · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential function in cell survival and is highly expressed in many cancers. Inhibition of TRPM2 in neuroblastoma by depletion with CRISPR technology or expression of dominant negative TRPM2-S has been shown to significantly reduce cell viability. Here, the role of proline-rich tyrosine kinase 2 (Pyk2) in TRPM2 modulation of neuroblastoma viability was explored. In TRPM2-depleted cells, phosphorylation and expression of Pyk2 and cAMP-responsive element-binding protein (CREB), a downstream target, were significantly reduced after application of the chemotherapeutic agent doxorubicin. Overexpression of wild-type Pyk2 rescued cell viability. Reduction of Pyk2 expression with shRNA decreased cell viability and CREB phosphorylation and expression, demonstrating Pyk2 modulates CREB activation. TRPM2 depletion impaired phosphorylation of Src, an activator of Pyk2, and this may be a mechanism to reduce Pyk2 phosphorylation. TRPM2 inhibition was previously demonstrated to decrease mitochondrial function. Here, CREB, Pyk2, and phosphorylated Src were reduced in mitochondria of TRPM2-depleted cells, consistent with their role in modulating expression and activation of mitochondrial proteins. Phosphorylated Src and phosphorylated and total CREB were reduced in TRPM2-depleted nuclei. Expression and function of mitochondrial calcium uniporter (MCU), a target of phosphorylated Pyk2 and CREB, were significantly reduced. Wild-type TRPM2 but not Ca
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