Lipid rafts mediates signaling pathway to cellular senescence induced by ionizing radiation exposure

초록

Cellular senescence is a state of irreversible cell growth arrest that occurs when cells experience potentially oncogenic stress. In addition, senescence can be stimulated by diverse factors, such as telomere dysfunction and oxidative damage, as well as the DNA damage response caused by ionizing radiation (IR) and chemotherapeutic drugs. Lipid rafts, microdomains of plasma membrane, are enriched in cholesterol and glycosphingolipids, are known to be abundant in various signaling molecules. These microdomains have been involved in many cellular functions, including apoptosis, cell proliferation, cell signaling, and others. Even though it has been suggested that lipid rafts play important roles in chemo- and radio-resistance during cancer treatment, the role of lipid rafts on IR-induced cellular senescence is less defined. In this study, we report that lipid rafts increased during IR-induced cellular senescence in A549 human lung carcinoma cells. When lipid rafts were disrupted using MβCD or lovastatin, IR-induced senescence phenotypes disappeared. We also found that disruption of lipid rafts switches cell fate from senescence to apoptosis in cancer cells exposed to IR. Collectively, the composition of lipid rafts might involve in IR-induced cellular senescence.