Transient receptor potential cation 3 channel regulates melanoma proliferation and migration.
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.
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.|Department of Environmental Immune-Dermatology, Yokohama City University School of Medicine, Yokohama, Japan.
Kayoko
K
Oda
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. umemurma@yokohama-cu.ac.jp.
Masanari
http://orcid.org/0000-0002-1812-5720
M
Umemura
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Rina
R
Nakakaji
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Ryo
R
Tanaka
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Itaru
I
Sato
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Akane
A
Nagasako
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Chiaki
C
Oyamada
Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, USA.
Erdene
E
Baljinnyam
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Mayumi
M
Katsumata
Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, USA.
Lai-Hua
LH
Xie
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Masatoshi
M
Narikawa
Department of Environmental Immune-Dermatology, Yokohama City University School of Medicine, Yokohama, Japan.
Yukie
Y
Yamaguchi
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Taisuke
T
Akimoto
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Makoto
M
Ohtake
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Takayuki
T
Fujita
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Utako
U
Yokoyama
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.|South Miyazaki Kidney Clinic, Miyazaki, Japan.
Kousaku
K
Iwatsubo
Department of Environmental Immune-Dermatology, Yokohama City University School of Medicine, Yokohama, Japan.
Michiko
M
Aihara
Cardiovascular Research Institute, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. yishikaw@med.yokohama-cu.ac.jp.
Yoshihiro
Y
Ishikawa
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D034622:RNA Interference; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D011720:Pyrazoles; D050799:STAT5 Transcription Factor; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C559943:ethyl-1-(4-(2*3*3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate; D051057:Proto-Oncogene Proteins c-akt
Melanoma; Metastasis; Migration; Proliferation; Pyr3; TRPC3