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Updated: Mar 15, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Transient receptor potential cation 3 channel regulates melanoma proliferation and migration
Kayoko Oda1,2, Masanari Umemura3, Rina Nakakaji1
1Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Abstract:
Melanoma has an extremely poor prognosis due to its rapidly progressive and highly metastatic nature. Several therapeutic drugs have recently become available, but are effective only against melanoma with specific BRAF gene mutation. Thus, there is a need to identify other target molecules. We show here that Transient receptor potential, canonical 3 (TRPC3) is widely expressed in human melanoma. We found that pharmacological inhibition of TRPC3 with a pyrazole compound, Pyr3, decreased melanoma cell proliferation and migration. Similar inhibition was observed when the TRPC3 gene was silenced with short-hairpin RNA (shRNA). Pyr3 induced dephosphorylation of signal transducer and activator of transcription (STAT) 5 and Akt. Administration of Pyr3 (0.05 mg/kg) to mice implanted with human melanoma cells (C8161) significantly inhibited tumor growth. Our findings indicate that TRPC3 plays an important role in melanoma growth, and may be a novel target for treating melanoma in patients.
Insights
Targeting Transient receptor potential, canonical 3 (TRPC3) shows promise for melanoma treatment. Inhibiting TRPC3 with Pyr3 reduced melanoma cell growth and migration in preclinical models, suggesting TRPC3 as a novel therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Melanoma is aggressive and metastatic, with limited treatment options for BRAF wild-type cases.
- There is a critical need for novel therapeutic targets beyond BRAF mutations.
Purpose of the Study:
- To investigate the role of Transient receptor potential, canonical 3 (TRPC3) in melanoma.
- To evaluate TRPC3 as a potential therapeutic target for melanoma treatment.
Main Methods:
- Assessed TRPC3 expression in human melanoma tissues.
- Utilized pharmacological inhibition (Pyr3) and genetic silencing (shRNA) of TRPC3.
- Examined effects on melanoma cell proliferation, migration, and downstream signaling pathways (STAT5, Akt).
- Evaluated Pyr3 efficacy in a murine melanoma xenograft model.
Main Results:
- TRPC3 is widely expressed in human melanoma.
- Pharmacological inhibition and genetic silencing of TRPC3 significantly reduced melanoma cell proliferation and migration.
- Pyr3 treatment led to dephosphorylation of STAT5 and Akt.
- In vivo administration of Pyr3 inhibited melanoma tumor growth in mice.
Conclusions:
- TRPC3 plays a crucial role in melanoma progression.
- TRPC3 represents a promising novel therapeutic target for melanoma treatment.
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