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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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 recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/62681
Acceso en línea:https://doi.org/10.1111/pcmr.12690
http://hdl.handle.net/10459.1/62681
Access Level:acceso abierto
Palabra clave:Melanoma
T-Type Calcium channels
Autophagy
Migration
Invasion
BRAFV600E
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repository_id_str
spelling T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1Maiques Carlos, OscarBarceló Gómez, CarlaPanosa, AnaisPijuan Marquilles, JordiOrgaz, Jose L.Rodríguez Hernández, IreneMatas Nadal, ClaraTell, GemmaVilella, RamónFabra, AngelsPuig, SusanaSanz Moreno, VictoriaMatias-Guiu, XavierCantí Nicolás, CarlesHerreros Danés, JuditMartí Laborda, Rosa Ma.Macià Armengol, AnnaMelanomaT-Type Calcium channelsAutophagyMigrationInvasionBRAFV600EMelanoma 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).Supported by grants from ISCIII/FEDER “Una manera de hacer Europa” (FIS-PI1200260 and PI1500711 to RMM, PI1301980 to JH and CIBERONC-CB16/12/00231 to XMG), Fundació la Marató de TV3 (FMTV 201331-30 to SP, -31 to RMM, and -32 to AF), Generalitat de Catalunya (2014/SGR138 to XMG); and Cancer Research UK grants C33043/A12065 and C33043/A24478 (VSM, JLO). OM holds a predoctoral fellowship from IRBLleida/Diputació de Lleida and CB a predoctoral fellowship from University of Lleida. AM holds a postdoctoral fellowship from AECC Scientific Foundation. IRH is supported by Marie Sklodowska-Curie Action (H2020-MSCA-IF-2014-EF-ST). Tumor samples were obtained with the support of Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncologia de Catalunya (XBTC) and IRBLleida Biobank (B.0000682) and PLATAFORMA BIOBANCOS (PT17/0015/0027).Wiley2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttps://doi.org/10.1111/pcmr.12690http://hdl.handle.net/10459.1/62681reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a https://doi.org/10.1111/pcmr.12690Pigment Cell and Melanoma Research, 2018, vol. 31, núm. 4, p. 484-495(c) Wiley, 2018info:eu-repo/semantics/openAccessoai:recercat.cat:10459.1/626812026-05-29T05:05:01Z
dc.title.none.fl_str_mv T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
title T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
spellingShingle T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
Maiques Carlos, Oscar
Melanoma
T-Type Calcium channels
Autophagy
Migration
Invasion
BRAFV600E
title_short T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
title_full T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
title_fullStr T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
title_full_unstemmed T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
title_sort T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
dc.creator.none.fl_str_mv 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
author Maiques Carlos, Oscar
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Melanoma
T-Type Calcium channels
Autophagy
Migration
Invasion
BRAFV600E
topic Melanoma
T-Type Calcium channels
Autophagy
Migration
Invasion
BRAFV600E
description 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).
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1111/pcmr.12690
http://hdl.handle.net/10459.1/62681
url https://doi.org/10.1111/pcmr.12690
http://hdl.handle.net/10459.1/62681
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a https://doi.org/10.1111/pcmr.12690
Pigment Cell and Melanoma Research, 2018, vol. 31, núm. 4, p. 484-495
dc.rights.none.fl_str_mv (c) Wiley, 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Wiley, 2018
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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