Galectin-3 sensitized melanoma cell lines to vemurafenib (PLX4032) induced cell death through prevention of autophagy

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art_BUSTOS_Galectin3_sensitized_melanoma_cell_lines_to_vemurafenib_PLX4032_2018.PDF (2.61 MB)
Citações na Scopus
21
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
IMPACT JOURNALS LLC
Autores
PEREIRA, G. J. S.
GIL, C. D.
SMAILI, S. S.
Citação
ONCOTARGET, v.9, n.18, p.14567-14579, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Melanoma is a current worldwide problem, as its incidence is increasing. In the last years, several studies have shown that melanoma cells display high levels of autophagy, a self-degradative process that can promote survival leading to drug resistance. Consequently, autophagy regulation represents a challenge for cancer therapy. Herein, we showed that galectin-3 (Gal-3), a β-galactoside binding lectin which is often lost along melanoma progression, is a negative regulator of autophagy in melanoma cells. Our data demonstrated that Gal-3low/negative cells were more resistant to the inhibition of the activity of the cancer driver gene BRAFV600E by vemurafenib (PLX4032). Interestingly, in these cells, starvation caused further LC3-II accumulation in cells exposed to chloroquine, which inhibits the degradative step in autophagy. In addition, Gal-3 low/negative tumor cells accumulated more LC3-II than Gal-3 high tumor cells in vivo. Resistance of Gal-3low/negative cells was associated with increased production of superoxide and activation of the Endoplasmic Reticulum (ER) stress response, as evaluated by accumulation of GRP78. Pharmacological inhibition of autophagy with bafilomycin A reversed the relative resistance of Gal-3low/negative cells to vemurafenib treatment. Taken together, these results show that the autophagic flux is dependent on Gal-3 levels, which attenuate the prosurvival role of autophagy. © Bustos et al.
Palavras-chave
Autophagy, Galectin-3, Melanoma, Starvation, Vemurafenib
URI
https://observatorio.fm.usp.br/handle/OPI/31030
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Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - HC/ICESP
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Artigos e Materiais de Revistas Científicas - ODS/03