Concurrent MEK and autophagy inhibition is required to restore cell death associated danger-signalling in Vemurafenib-resistant melanoma cells

Martin, S.; Dudek-Peric, A.; Maes, H.; Garg, A.; Gabrysiak, M.; Demirsoy, ŞEYMA; Swinnen, J.; Agostinis, P.

doi:10.1016/j.bcp.2014.12.003

Concurrent MEK and autophagy inhibition is required to restore cell death associated danger-signalling in Vemurafenib-resistant melanoma cells

Martin S., Dudek-Peric A. M., Maes H., Garg A. D., Gabrysiak M., Demirsoy S., ...More

BIOCHEMICAL PHARMACOLOGY, vol.93, no.3, pp.290-304, 2015 (SCI-Expanded, Scopus)

Publication Type: Article / Article
Volume: 93 Issue: 3
Publication Date: 2015
Doi Number: 10.1016/j.bcp.2014.12.003
Journal Name: BIOCHEMICAL PHARMACOLOGY
Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
Page Numbers: pp.290-304
Open Archive Collection: AVESIS Open Access Collection
Hacettepe University Affiliated: No

Abstract

Vemurafenib (PLX4032), an inhibitor of BRAF(V600E), has demonstrated significant clinical anti-melanoma effects. However, the majority of treated patients develop resistance, due to a variety of molecular mechanisms including MAPK reactivation through MEK. The induction of a cancer cell death modality associated with danger-signalling resulting in surface mobilization of crucial damage-associated-molecular-patterns (DAMPs), e.g. calreticulin (CRT) and heat shock protein-90 (HSP90), from dying cells, is emerging to be crucial for therapeutic success. Both cell death and danger-signalling are modulated by autophagy, a key adaptation mechanism stimulated during melanoma progression. However, whether melanoma cell death induced by MAPK inhibition is associated with danger-signalling, and the reliance of these mechanisms on autophagy, has not yet been scrutinized.