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https://observatorio.fm.usp.br/handle/OPI/31030
Title: | Galectin-3 sensitized melanoma cell lines to vemurafenib (PLX4032) induced cell death through prevention of autophagy |
Authors: | BUSTOS, S. O.; PEREIRA, G. J. S.; SAITO, R. F.; GIL, C. D.; ZANATTA, D. B.; SMAILI, S. S.; CHAMMAS, R. |
Citation: | ONCOTARGET, v.9, n.18, p.14567-14579, 2018 |
Abstract: | 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. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MDR Artigos e Materiais de Revistas Científicas - HC/ICESP Artigos e Materiais de Revistas Científicas - LIM/24 Artigos e Materiais de Revistas Científicas - ODS/03 |
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art_BUSTOS_Galectin3_sensitized_melanoma_cell_lines_to_vemurafenib_PLX4032_2018.PDF | publishedVersion (English) | 2.67 MB | Adobe PDF | View/Open |
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