Cellular senescence is a biologically irreversible state of cell-growth arrest that occurs following either a replicative or an oncogenic stimulus. This phenomenon occurs as a response to the presence of premalignant cells and appears to be an important anticancer mechanism that keeps these transformed cells at bay. Many exogenous and endogenous triggers for senescence have been recognized to act via genomic or epigenomic pathways. The most common stimulus for senescence is progressive loss of telomeric DNA, which results in the loss of chromosomal stability and eventual unregulated growth and malignancy. Senescence is activated through an interaction between the p16 and p53 tumor-suppressor genes. Senescent cells can be identified in vitro because they express senescence-associated beta-galactosidase, a marker of increased lysosomal activity. Cellular senescence plays an integral role in the prevention and development of both benign and malignant gastrointestinal diseases. The senescence cascade and the cell-cycle checkpoints that dictate the progression and maintenance of senescence are important in all types of gastrointestinal cancers, including pancreatic, liver, gastric, colon, and esophageal cancers. Understanding the pathogenic mechanisms involved in cellular senescence is important for the development of agents targeted toward the treatment of gastrointestinal tumors.
Aging ; Bays ; beta-Galactosidase ; Cell Aging ; Chromosomal Instability ; Colon ; DNA ; Epigenomics ; Esophageal Neoplasms ; Gastrointestinal Diseases ; Gastrointestinal Neoplasms ; Liver ; Mucous Membrane