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. , ...Daha Fazla

BIOCHEMICAL PHARMACOLOGY, cilt.93, sa.3, ss.290-304, 2015 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 93 Konu: 3
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.bcp.2014.12.003
  • Dergi Adı: BIOCHEMICAL PHARMACOLOGY
  • Sayfa Sayıları: ss.290-304

Özet

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.