Abstract
Impaired ability to undergo programmed cell death in response to a wide range of external stimuli acquires melanomas a selective advantage for progression and metastasis as well as their notorious resistance to therapy. Better understanding of mechanisms that govern apoptosis has enabled identification of diverse routes by which melanomas manage to escape stimuli of apoptosis. Changes at genomic, transcriptional and post-translational levels of G-proteins and protein kinases (Ras, B-Raf) and their transcription factor effectors (c-Jun, ATF2, Stat3 and NF-kappaB) affects TNF, Fas and TRAIL receptors, which play important roles in acquiring melanoma's resistance to apoptosis. Here, we summarize our current understanding of changes that alters the regulation of death receptors during melanoma development.
MeSH Terms
Activating Transcription Factor 2
Animals
Antigens, CD/genetics,metabolism
Apoptosis/drug effects,physiology
Apoptosis Regulatory Proteins
CASP8 and FADD-Like Apoptosis Regulating Protein
Carrier Proteins/genetics,metabolism
Cyclic AMP Response Element-Binding Protein/antagonists & inhibitors,metabolism
Drug Resistance, Neoplasm/physiology
Humans
Intracellular Signaling Peptides and Proteins
Melanoma/drug therapy,metabolism,pathology
Membrane Glycoproteins/metabolism
NF-kappa B/drug effects,metabolism
Proto-Oncogene Proteins c-jun/genetics,metabolism
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor/genetics,metabolism
Receptors, Tumor Necrosis Factor, Type I
Signal Transduction
TNF-Related Apoptosis-Inducing Ligand
Transcription Factors/antagonists & inhibitors,drug effects,genetics,metabolism
Tumor Necrosis Factor-alpha/metabolism
Tumor Suppressor Protein p53/genetics,metabolism
fas Receptor/drug effects,metabolism
Chemicals
ATF2 protein, human
Activating Transcription Factor 2
Antigens, CD
Apoptosis Regulatory Proteins
CASP8 and FADD-Like Apoptosis Regulating Protein
CFLAR protein, human
Carrier Proteins
Cyclic AMP Response Element-Binding Protein
Intracellular Signaling Peptides and Proteins
Membrane Glycoproteins
NF-kappa B
Proto-Oncogene Proteins c-jun
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
TNF-Related Apoptosis-Inducing Ligand
TNFRSF10A protein, human
TNFSF10 protein, human
Transcription Factors
Tumor Necrosis Factor-alpha
Tumor Suppressor Protein p53
fas Receptor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ivanov Vladimir N
Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Bhoumik Anindita
Ronai Ze'ev