Sustained activation of DNA damage response in irradiated apoptosis-resistant cells induces reversible senescence associated with mTOR downregulation and expression of stem cell markers.

摘要: Cells respond to genotoxic stress by activating the DNA damage response (DDR). When injury is severe or irreparable, cells induce apoptosis cellular senescence prevent transmission of lesions daughter upon cell division. Resistance a hallmark cancer that challenges efficacy therapy. In this work, effects ionizing radiation on apoptosis-resistant E1A + E1B transformed were investigated ascertain whether activation could provide an alternative tumor suppressor mechanism. We show irradiated arrest cycle at G2/M phase and resume replication in absence division followed formation giant polyploid cells. Permanent DDR signaling due impaired repair results induction However, bypass restore population dividing cells, which have near normal size ploidy do not express markers. Reversion appearance proliferating associated with downregulation mTOR, autophagy, mitigation signaling, expression stem