Transient receptor potential cation 3 channel regulates melanoma proliferation and migration

被引：34

作者：

Oda, Kayoko ^{[1
,2
]}

Umemura, Masanari ^{[1
]}

Nakakaji, Rina ^{[1
]}

Tanaka, Ryo ^{[1
]}

Sato, Itaru ^{[1
]}

Nagasako, Akane ^{[1
]}

Oyamada, Chiaki ^{[1
]}

Baljinnyam, Erdene ^{[3
]}

Katsumata, Mayumi ^{[1
]}

Xie, Lai-Hua ^{[3
]}

Narikawa, Masatoshi ^{[1
]}

Yamaguchi, Yukie ^{[2
]}

Akimoto, Taisuke ^{[1
]}

Ohtake, Makoto ^{[1
]}

Fujita, Takayuki ^{[1
]}

Yokoyama, Utako ^{[1
]}

Iwatsubo, Kousaku ^{[1
,4
]}

Aihara, Michiko ^{[2
]}

Ishikawa, Yoshihiro ^{[1
]}

机构：

[1] Yokohama City Univ, Sch Med, Cardiovasc Res Inst, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan

[2] Yokohama City Univ, Sch Med, Dept Environm Immunedermatol, Yokohama, Kanagawa, Japan

[3] Rutgers State Univ, Dept Cell Biol & Mol Med, New Jersey Med Sch, Newark, NJ USA

[4] South Miyazaki Kidney Clin, Miyazaki, Japan

来源：

JOURNAL OF PHYSIOLOGICAL SCIENCES | 2017年 / 67卷 / 04期

基金：

日本学术振兴会;

关键词：

TRPC3; Proliferation; Migration; Melanoma; Metastasis; Pyr3; CELL MIGRATION; CA2+ ENTRY; SURVIVAL; DELIVERY; STORE; TRPC3; SRC;

D O I：

10.1007/s12576-016-0480-1

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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.

引用

收藏

页码：497 / 505

页数：9

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