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Updated: Feb 12, 2026

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
Downregulated TRPV1 Expression Contributes to Melanoma Growth via the Calcineurin-ATF3-p53 Pathway
Yuqi Yang1, Weinan Guo1, Jingjing Ma1
1Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Abstract:
Melanoma is the most lethal form of skin cancer with increasing incidence over the years. Because of its rapid proliferative and drastic metastatic capacity, the prognosis of melanoma remains dismal, although the targeted therapy and immunotherapy have gained revolutionary progress recently. Therefore, it is of necessity to further clarify the mechanism of melanoma pathogenesis for developing an alternative treatment strategy. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective Ca2+ channel greatly involved in regulating cell apoptosis, proliferation, metabolism, and cancer development, but its role in melanoma remains unknown. Herein, we first found that TRPV1 expression was significantly decreased in melanoma tissues and cell lines, compared with nevus tissues and normal melanocytes, respectively. We then proved that TRPV1 overexpression or its agonist capsaicin treatment inhibited melanoma growth by activating p53 and inducing cell apoptosis. A subsequent mechanistic study revealed that TRPV1 induced Ca2+ influx to regulate p53 activation via calcineurin-ATF3 transcriptional cascade. Finally, the effect of TRPV1 on melanoma growth was proved in vivo. Altogether, our study demonstrates that TRPV1 is a potential tumor suppressor in melanoma.
Insights
Transient receptor potential vanilloid 1 (TRPV1) acts as a tumor suppressor in melanoma. Lower TRPV1 expression correlates with melanoma, and its activation inhibits cancer growth by inducing apoptosis via p53.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Melanoma is an aggressive skin cancer with poor prognosis despite recent therapeutic advances.
- Understanding melanoma pathogenesis is crucial for developing novel treatments.
- The role of Transient Receptor Potential Vanilloid 1 (TRPV1) in melanoma is currently unknown.
Purpose of the Study:
- To investigate the role of TRPV1 in melanoma development and progression.
- To determine if TRPV1 expression is altered in melanoma tissues.
- To explore TRPV1's potential as a therapeutic target in melanoma.
Main Methods:
- Quantitative analysis of TRPV1 expression in melanoma tissues and cell lines versus normal controls.
- In vitro studies involving TRPV1 overexpression and capsaicin treatment in melanoma cells.
- Investigation of downstream signaling pathways, including p53 activation and apoptosis induction.
- In vivo studies to confirm the effect of TRPV1 on melanoma growth.
Main Results:
- TRPV1 expression was significantly downregulated in melanoma tissues and cell lines compared to nevus tissues and normal melanocytes.
- Overexpression of TRPV1 or treatment with the agonist capsaicin inhibited melanoma cell proliferation and induced apoptosis.
- TRPV1 activation led to increased intracellular calcium (Ca2+), which in turn activated p53 through the calcineurin-ATF3 pathway.
- In vivo experiments confirmed that TRPV1 suppresses melanoma tumor growth.
Conclusions:
- TRPV1 functions as a tumor suppressor in melanoma.
- Reduced TRPV1 expression is associated with melanoma.
- TRPV1 activation represents a potential therapeutic strategy for melanoma treatment.
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