Transient receptor potential cation 3 channel regulates melanoma proliferation and migration.

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.

• Authors: Kayoko Oda, Masanari Umemura, Rina Nakakaji, Ryo Tanaka, Itaru Sato, Akane Nagasako, Chiaki Oyamada, Erdene Baljinnyam, Mayumi Katsumata, Lai-Hua Xie, Masatoshi Narikawa, Yukie Yamaguchi, Taisuke Akimoto, Makoto Ohtake, Takayuki Fujita, Utako Yokoyama, Kousaku Iwatsubo, Michiko Aihara, Yoshihiro Ishikawa
• Journal: The journal of physiological sciences : JPS (J Physiol Sci) Vol. 67 Issue 4 Pg. 497-505 (Jul 2017) ISSN: 1880-6562 [Electronic] Japan
• PMID: 27613608 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Pyrazoles
• STAT5 Transcription Factor
• TRPC Cation Channels
• TRPC3 cation channel
• ethyl-1-(4-(2*3*3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Melanoma (drug therapy, genetics, metabolism, pathology)
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyrazoles (pharmacology)
• RNA Interference
• STAT5 Transcription Factor (metabolism)
• Signal Transduction
• Skin Neoplasms (drug therapy, genetics, metabolism, pathology)
• TRPC Cation Channels (antagonists & inhibitors, genetics, metabolism)
• Time Factors
• Transfection
• Xenograft Model Antitumor Assays