Senescence as a modulator of oral squamous cell carcinoma development.
Senescence of somatic cells in vitro can occur through the gradual erosion of the chromosomal telomeres following multiple rounds of cell division, or more acutely following cellular stresses connected with oncogene activation, tumour suppressor loss, ageing and migration. These various forms of senescence are associated with the activation of DNA damage checkpoints, the over-expression of p16(INK4A) and the secretion of cytokines, all of which are detected in pre-malignant lesions but muted upon malignant conversion. The various senescence signals are integrated by p16(INK4A) and p53 to produce the permanent cell cycle arrest associated with senescence. Both pRB/p16(INK4A) and p53 are dysfunctional in many cancers, including the most common type of oral cancer, squamous cell carcinoma (OSCC) and other evidence is accumulating in support of the idea that senescence acts as a barrier to tumour development and/or progression. However, senescence of the non-epithelial component of developing human tumours has been shown to enhance growth and invasion of the pre-malignant epithelial component and so senescence may well enhance cancer as well as suppress it depending on the context.
Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, England, UK. e.k.parkinson@qmul.ac.uk
E Kenneth
EK
Parkinson
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D005260:Female; D019942:Genes, p16 / Q000502:physiology*; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D016159:Tumor Suppressor Protein p53