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

Oscar Maiques; Carla Barceló; Anaïs Panosa; Jordi Pijuan; Jose L. Orgaz; Irene Rodriguez-Hernandez; Clara Matas-Nadal; Gemma Tell; Ramón Vilella; Angels Fabra; Susana Puig; Victoria Sanz-Moreno; Xavier Matias-Guiu; Carles Canti; Judit Herreros; Rosa M. Marti; Anna Macià

doi:10.1111/pcmr.12690

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

Oscar Maiques, Carla Barceló, Anaïs Panosa, Jordi Pijuan, Jose L. Orgaz, Irene Rodriguez-Hernandez, Clara Matas-Nadal, Gemma Tell, Ramón Vilella, Angels Fabra, Susana Puig, Victoria Sanz-Moreno, Xavier Matias-Guiu, Carles Canti, Judit Herreros, Rosa M. Marti, Anna Macià^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

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).

Original language	English
Journal	Pigment Cell and Melanoma Research
Early online date	18 Feb 2018
DOIs	https://doi.org/10.1111/pcmr.12690
Publication status	E-pub ahead of print - 18 Feb 2018

Keywords

Autophagy
BRAFV600E
Melanoma
Migration/invasion
T-type calcium channels

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/pcmr.12690

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Maiques, O., Barceló, C., Panosa, A., Pijuan, J., Orgaz, J. L., Rodriguez-Hernandez, I., Matas-Nadal, C., Tell, G., Vilella, R., Fabra, A., Puig, S., Sanz-Moreno, V., Matias-Guiu, X., Canti, C., Herreros, J., Marti, R. M., & Macià, A. (2018). T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1. Pigment Cell and Melanoma Research. Advance online publication. https://doi.org/10.1111/pcmr.12690

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title = "T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1",

abstract = "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).",

keywords = "Autophagy, BRAFV600E, Melanoma, Migration/invasion, T-type calcium channels",

author = "Oscar Maiques and Carla Barcel{\'o} and Ana{\"i}s Panosa and Jordi Pijuan and Orgaz, {Jose L.} and Irene Rodriguez-Hernandez and Clara Matas-Nadal and Gemma Tell and Ram{\'o}n Vilella and Angels Fabra and Susana Puig and Victoria Sanz-Moreno and Xavier Matias-Guiu and Carles Canti and Judit Herreros and Marti, {Rosa M.} and Anna Maci{\`a}",

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month = feb,

day = "18",

doi = "10.1111/pcmr.12690",

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Maiques, O, Barceló, C, Panosa, A, Pijuan, J, Orgaz, JL , Rodriguez-Hernandez, I, Matas-Nadal, C, Tell, G, Vilella, R, Fabra, A, Puig, S, Sanz-Moreno, V, Matias-Guiu, X, Canti, C, Herreros, J, Marti, RM & Macià, A 2018, 'T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1', Pigment Cell and Melanoma Research. https://doi.org/10.1111/pcmr.12690

TY - JOUR

T1 - T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1

AU - Maiques, Oscar

AU - Barceló, Carla

AU - Panosa, Anaïs

AU - Pijuan, Jordi

AU - Orgaz, Jose L.

AU - Rodriguez-Hernandez, Irene

AU - Matas-Nadal, Clara

AU - Tell, Gemma

AU - Vilella, Ramón

AU - Fabra, Angels

AU - Puig, Susana

AU - Sanz-Moreno, Victoria

AU - Matias-Guiu, Xavier

AU - Canti, Carles

AU - Herreros, Judit

AU - Marti, Rosa M.

AU - Macià, Anna

PY - 2018/2/18

Y1 - 2018/2/18

N2 - 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).

AB - 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).

KW - Autophagy

KW - BRAFV600E

KW - Melanoma

KW - Migration/invasion

KW - T-type calcium channels

UR - http://www.scopus.com/inward/record.url?scp=85042121029&partnerID=8YFLogxK

U2 - 10.1111/pcmr.12690

DO - 10.1111/pcmr.12690

M3 - Article

AN - SCOPUS:85042121029

SN - 1755-1471

JO - Pigment Cell and Melanoma Research

JF - Pigment Cell and Melanoma Research

ER -

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

Abstract

Keywords

UN SDGs

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