ArticleThe Journal of cell biology2017
TRPM8 inhibits endothelial cell migration via a non-channel function by trapping the small GTPase Rap1.
Article in The Journal of cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- Hydrogel-Based Delivery of Ion Channel Modulators for Cancer Therapy: Current Advances and Future Perspectives.Gels (Basel, Switzerland) · 2026Review
- Direct crosstalk between GPCRs and ion channels via G proteins.Experimental & molecular medicine · 2025Review
- Functionally enriched human polymorphisms associate to species in the chronic wound microbiome.NPJ biofilms and microbiomes · 2025Article
- TRP channels and cancer modulation: a voyage beyond metabolic reprogramming, oxidative stress and the advent of nanotechnologies in targeted therapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025Review
- Article
- Cell communication and relevant signaling pathways in osteogenesis-angiogenesis coupling.Bone research · 2025Review
- Multiple Hub Genes as Diagnostic and Therapeutic Targets Inducing Inflammation and Angiogenesis in Retinopathy of Prematurity.International journal of general medicine · 2025Article
- TRPM channels in human cancers: regulatory mechanism and therapeutic prospects.Biomarker research · 2024Review
- Integrins regulate hERG1 dynamics by girdin-dependent Gαi3: signaling and modeling in cancer cells.Life science alliance · 2024Article
- Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets.PloS one · 2024Article
- Cold temperature induces a TRPM8-independent calcium release from the endoplasmic reticulum in human platelets.bioRxiv : the preprint server for biology · 2023Article
- JP1 normalizes tumor vasculature to suppress metastasis and facilitate drug delivery by inhibiting IL-8.JCI insight · 2023Article
- Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells.Cells · 2023Review
- Effect of TRPM8 Functional Loss on Corneal Epithelial Wound Healing in Mice.Investigative ophthalmology & visual science · 2023Article
- Intracellular CaFrontiers in physiology · 2023Review
- Transient Receptor Potential (TRP) Channels in Tumor Vascularization.International journal of molecular sciences · 2022Review
- The cation channel TRPM8 influences the differentiation and function of human monocytes.Journal of leukocyte biology · 2022Article
- TRPM8 as an Anti-Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination.International journal of molecular sciences · 2022Article
- Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing cell motility. However, the mechanisms by which it could influence vascular behavior are unknown. Here, we reveal a novel non-channel function for TRPM8 that unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting endothelial cell motility, independently of pore function. TRPM8 retains Rap1 intracellularly through direct protein-protein interaction, thus preventing its cytoplasm-plasma membrane trafficking. In turn, this mechanism impairs the activation of a major inside-out signaling pathway that triggers the conformational activation of integrin and, consequently, cell adhesion, migration, in vitro endothelial tube formation, and spheroid sprouting. Our results bring to light a novel, pore-independent molecular mechanism by which endogenous TRPM8 expression inhibits Rap1 GTPase and thus plays a critical role in the behavior of vascular endothelial cells by inhibiting migration.
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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.