T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1

Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it is usually highly resistant to chemotherapy and is associated with poor prognosis. We have recently reported that T-type calcium channels (TTCCs) are overexpressed in melanoma cells and play an important role in melanoma p...

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Detalhes bibliográficos
Autores: Maiques Carlos, Oscar, Barceló Gómez, Carla, Panosa, Anais, Pijuan Marquilles, Jordi, Orgaz, Jose L., Rodríguez Hernández, Irene, Matas Nadal, Clara, Tell, Gemma, Vilella, Ramón, Fabra, Angels, Puig, Susana, Sanz Moreno, Victoria, Matias-Guiu, Xavier, Cantí Nicolás, Carles, Herreros Danés, Judit, Martí Laborda, Rosa Ma., Macià Armengol, Anna
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2018
País:España
Recursos:Universitat de Lleida (UdL)
Repositório:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/62681
Acesso em linha:https://doi.org/10.1111/pcmr.12690
http://hdl.handle.net/10459.1/62681
Access Level:Acceso aberto
Palavra-chave:Melanoma
T-Type Calcium channels
Autophagy
Migration
Invasion
BRAFV600E
Descrição
Resumo:Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it is usually highly resistant to chemotherapy and is associated with poor prognosis. We have recently reported that T-type calcium channels (TTCCs) are overexpressed in melanoma cells and play an important role in melanoma progression. Importantly, TTCC pharmacological blockers reduce proliferation and deregulate autophagy leading to apoptosis. Here, we analyze the role of autophagy during migration/invasion of melanoma cells. TTCC Cav3.1 and LC3-II proteins are highly expressed in BRAFV600E compared with NRAS mutant melanomas, both in cell lines and biopsies. Chloroquine, pharmacological blockade, or gene silencing of TTCCs inhibit the autophagic flux and impair the migration and invasion capabilities, specifically in BRAFV600E melanoma cells. Snail1 plays an important role in motility and invasion of melanoma cells. We show that Snail1 is strongly expressed in BRAFV600E melanoma cells and patient biopsies, and its expression decreases when autophagy is blocked. These results demonstrate a role of Snail1 during BRAFV600E melanoma progression and strongly suggest that targeting macroautophagy and, particularly TTCCs, might be a good therapeutic strategy to inhibit metastasis of the most common melanoma type (BRAFV600E).

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