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T‐type calcium channels drive migration/invasion in BRAFV 600E melanoma cells through Snail1
Author(s) -
Maiques Oscar,
Barceló Carla,
Panosa Anaïs,
Pijuan Jordi,
Orgaz Jose L.,
RodriguezHernandez Irene,
MatasNadal Clara,
Tell Gemma,
Vilella Ramón,
Fabra Angels,
Puig Susana,
SanzMoreno Victoria,
MatiasGuiu Xavier,
Canti Carles,
Herreros Judit,
Marti Rosa M.,
Macià Anna
Publication year - 2018
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12690
Subject(s) - melanoma , autophagy , cancer research , neuroblastoma ras viral oncogene homolog , gene silencing , biology , metastasis , apoptosis , cancer , mutation , gene , genetics , kras
Summary 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 ( TTCC s) 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 LC 3‐ II proteins are highly expressed in BRAFV 600E compared with NRAS mutant melanomas, both in cell lines and biopsies. Chloroquine, pharmacological blockade, or gene silencing of TTCC s inhibit the autophagic flux and impair the migration and invasion capabilities, specifically in BRAFV 600E melanoma cells. Snail1 plays an important role in motility and invasion of melanoma cells. We show that Snail1 is strongly expressed in BRAFV 600E melanoma cells and patient biopsies, and its expression decreases when autophagy is blocked. These results demonstrate a role of Snail1 during BRAFV 600E melanoma progression and strongly suggest that targeting macroautophagy and, particularly TTCC s, might be a good therapeutic strategy to inhibit metastasis of the most common melanoma type ( BRAFV 600E).