ArticleOncotarget2015
TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 85 citations in OpenAlex.
- Apoptosis of Mdm2-deficient osteocytes enhances osteogenesis through TRPM8-enriched apoptotic vesicles.Bone research · 2026Article
- Structural Modification of Selected Essential Oil Components for Potential Anticancer Applications: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Menthol and Its Derivatives: Exploring the Medical Application Potential.Engineering in life sciences · 2025Review
- An adamantane-based ligand as a novel chemical tool for thermosensory TRPM8 channel therapeutic modulation.The FEBS journal · 2025Article
- Article
- Calcium signalling pathways in prostate cancer initiation and progression.Nature reviews. Urology · 2023Review
- "ThermoTRP" Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist).International journal of molecular sciences · 2023Review
- TRPV6 Calcium Channel Targeting by Antibodies Raised against Extracellular Epitopes Induces Prostate Cancer Cell Apoptosis.Cancers · 2023Article
- Tissue immunostaining of candidate prognostic proteins in metastatic and non-metastatic prostate cancer.Journal of cancer research and clinical oncology · 2023Article
- Menthol: An underestimated anticancer agent.Frontiers in pharmacology · 2023Review
- Therapeutic potential of TRPM8 channels in cancer treatment.Frontiers in pharmacology · 2023Review
- The LCK-14-3-3ζ-TRPM8 axis regulates TRPM8 function/assembly and promotes pancreatic cancer malignancy.Cell death & disease · 2022Article
- Article
- Nuclear and Membrane Receptors for Sex Steroids Are Involved in the Regulation of Delta/Serrate/LAG-2 Proteins in Rodent Sertoli Cells.International journal of molecular sciences · 2022Article
- Endocrine Disruptors and Prostate Cancer.International journal of molecular sciences · 2022Review
- How Protein Methylation Regulates Steroid Receptor Function.Endocrine reviews · 2022Review
- On the modulation of TRPM channels: Current perspectives and anticancer therapeutic implications.Frontiers in oncology · 2022Review
- New Insights and Emerging Therapeutic Approaches in Prostate Cancer.Frontiers in endocrinology · 2022Review
- Therapeutic potential of TRPM8 antagonists in prostate cancer.Scientific reports · 2021Article
- Sex-Bias in Irritable Bowel Syndrome: Linking Steroids to the Gut-Brain Axis.Frontiers in endocrinology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The cold and menthol receptor TRPM8 is highly expressed in prostate and prostate cancer (PC). Recently, we identified that TRPM8 is as an ionotropic testosterone receptor. The TRPM8 mRNA is expressed in early prostate tumors with high androgen levels, while anti-androgen therapy greatly reduces its expression. Here, from the chromatin-immunoprecipitation (ChIP) analysis, we found that an androgen response element (ARE) mediates androgen regulation of trpm8. Furthermore, using immunofluorescence, calcium-imaging and planar lipid bilayers, we identified that TRPM8 channel is functionally regulated by androgens in the prostate. Although TRPM8 mRNA is expressed at high levels, we found that the TRPM8 protein undergoes ubiquitination and degradation in PC cells. The mass-spectrometry analysis of TRPM8, immunoprecipitated from LNCaP cells identified ubiquitin-like modifier-activating enzyme 1 (UBA1). PYR-41, a potent inhibitor of initial enzyme in the ubiquitination cascade, UBA1, increased TRPM8 activity on the plasma membrane (PM) of LNCaP cells. Furthermore, PYR-41-mediated PMTRPM8 activity was accompanied by enhanced activation of p53 and Caspase-9. Interestingly, we found that the trpm8 promoter possesses putative binding sites for p53 and that the overexpression of p53 increased the TRPM8 mRNA levels. In addition to the genomic regulation of TRPM8 by AR and p53, our findings indicate that the testosterone-induced PMTRPM8 activity elicits Ca2+ uptake, subsequently causing apoptotic cell death. These findings support the strategy of rescuing PMTRPM8 expression as a new therapeutic application through the regulation of PC cell growth and proliferation.
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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.