Senescence-Derived Extracellular Molecules as Modulators of Oral Cancer Development: A Mini-Review.

摘要: Oral cancers are predominantly oral squamous cell carcinomas (OSCCs) derived from keratinocytes, and there is now very detailed knowledge of the genetics molecular biology epithelial tumourigenic component these cancers, including identification cancer stem or tumour-initiating cells. Several key genetic alterations have been identified near ubiquitous loss CDKN2A/p16INK4A p53 pathways telomerase activation, together with frequent inactivation NOTCH1 canonical pathway either by somatic presence human papilloma virus. There also evidence that OSCCs arise a 'field' altered cells malignant conversion takes place pre-dominantly at microscopic level. However, in last decade, it has realised tumour development progression influenced microenvironment cross-talk between (tumour) mesenchymal components. OSCCs, especially those bypassed cellular senescence, produce an array proteins metabolites induce senescence normal surrounding cells; indeed, common property cancer-associated fibroblasts (CAFs). Cellular defined as irreversible cycle arrest associated release molecules known senescence-associated secretory phenotype can selectively promote growth pre-neoplastic keratinocytes (osteopontin) invasion (transforming factor β, matrix metalloproteinases, interleukin 6 lactate). In addition, both old new work shown harbouring NOTCH loss-of-function mutations lead to defective keratinocyte differentiation barrier function may act tumour-promoting stimulus for initiated RAS activating wound response mesenchyme. Thus, not all tissue be instead promoters analogous much-studied CAFs which co-evolve genetically This data discussed relation attempts develop novel non-invasive diagnostics therapeutics cancer.