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

Research output: Contribution to journalArticle

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

Original languageEnglish
JournalPigment Cell and Melanoma Research
Early online date18 Feb 2018
DOIs
Accepted/In press23 Dec 2017
E-pub ahead of print18 Feb 2018

King's Authors

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).

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