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.
Oral Oncol. 2010 Dec;46(12):840-53. doi: 10.1016/j.oraloncology.2009.09.009. Epub 2010 Nov 2.
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.
体外体细胞衰老可通过染色体端粒在多次细胞分裂后逐渐磨损而发生，或者在与癌基因激活、肿瘤抑制因子丧失、衰老和迁移相关的细胞应激下更迅速地发生。这些不同形式的衰老与 DNA 损伤检查点的激活、p16(INK4A)的过度表达和细胞因子的分泌有关，所有这些都在癌前病变中检测到，但在恶性转化时减弱。各种衰老信号被 p16(INK4A)和 p53 整合，产生与衰老相关的永久性细胞周期停滞。pRB/p16(INK4A)和 p53 在许多癌症中都存在功能障碍，包括最常见的口腔癌，鳞状细胞癌（OSCC），并且越来越多的证据支持衰老作为肿瘤发展和/或进展的障碍的观点。然而，已经表明，人类肿瘤的非上皮成分的衰老会增强癌前上皮成分的生长和侵袭，因此衰老可能会增强癌症，也可能会抑制癌症，具体取决于具体情况。
