TLR4 in skin cancer: From molecular mechanisms to clinical interventions

The health and economic burden imposed by skin cancer is substantial, creating an urgent need for the development of improved molecular strategies for its prevention and treatment. Cutaneous exposure to solar ultraviolet (UV) radiation is a causative factor in skin carcinogenesis, and TLR4‐dependent...

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Bibliographic Details
Published in:Molecular carcinogenesis 2019-07, Vol.58 (7), p.1086-1093
Main Authors: Dickinson, Sally E., Wondrak, Georg T.
Format: Article
Language:English
Subjects:
Carcinogenesis
Carcinogenesis - radiation effects
Carcinoma, Merkel Cell - pathology
Damage patterns
Environmental stress
Exposure
HMGB1 protein
Humans
Inflammation
Lipopolysaccharides
Melanoma
Melanoma - pathology
molecular intervention
Molecular modelling
Signal Transduction - drug effects
Skin - pathology
Skin cancer
Skin Neoplasms - pathology
Squamous Cell Carcinoma of Head and Neck - pathology
TLR4
TLR4 protein
Toll-Like Receptor 4 - metabolism
Toll-like receptors
Ultraviolet radiation
Ultraviolet Rays - adverse effects
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Summary:The health and economic burden imposed by skin cancer is substantial, creating an urgent need for the development of improved molecular strategies for its prevention and treatment. Cutaneous exposure to solar ultraviolet (UV) radiation is a causative factor in skin carcinogenesis, and TLR4‐dependent inflammatory dysregulation is an emerging key mechanism underlying detrimental effects of acute and chronic UV exposure. Direct and indirect TLR4 activation, upstream of inflammatory signaling, is elicited by a variety of stimuli, including pathogen‐associated molecular patterns (such as lipopolysaccharide) and damage‐associated molecular patterns (such as HMGB1) that are formed upon exposure to environmental stressors, such as solar UV. TLR4 involvement has now been implicated in major types of skin malignancies, including nonmelanoma skin cancer, melanoma and Merkel cell carcinoma. Targeted molecular interventions that positively or negatively modulate TLR4 signaling have shown promise in translational, preclinical, and clinical investigations that may benefit skin cancer patients in the near future.
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.23016