Nam, Hae Yun Han, Myung Woul Chang, Hyo Won Kim, Sang Yoon Kim, Seong Who 2024-01-20T11:30:29Z 2024-01-20T11:30:29Z 2021-09-05 2013-10-01 1554-8627 https://pubs.kist.re.kr/handle/201004/127553 Radiotherapy is one of the well-established therapeutic modalities for cancer treatment. However, the emergence of cells refractory to radiation is a major obstacle to successful treatment with radiotherapy. Many reports suggest that inhibitors targeting the mechanistic target of rapamycin (MTOR) can sensitize cancer cells to the effect of radiation, although by which mechanism MTOR inhibitors enhance the efficacy of radiation toward cancer cells remains to be elucidated. Our studies indicate that a potent and persistent activation of autophagy via inhibition of the MTOR pathway, even in cancer cells where autophagy is occurring, can trigger premature senescence, cellular proliferation arrest. Combined treatment of MTOR inhibitor and radiation induce heterochromatin formation, an irreversible growth arrest and an increase of senescence-associated GLB1 (-galactosidase) activity, which appear to result from a constant activation of TP53 and a restoration in the activity of retinoblastoma 1 protein (RB1)-E2F1. Thus, this study provides evidence that promoting cellular senescence via inhibition of the MTOR pathway may serve as an avenue to augment radiosensitivity in cancer cells that initiate an autophagy-survival mode to radiotherapy. English LANDES BIOSCIENCE Prolonged autophagy by MTOR inhibitor leads radioresistant cancer cells into senescence Article 10.4161/auto.25879 1 AUTOPHAGY, v.9, no.10, pp.1631 - 1632 AUTOPHAGY 9 10 1631 1632 scie scopus 000327579000019 2-s2.0-84885574879 Cell Biology Cell Biology Editorial Material MTOR inhibitor irradiation cellular senescence autophagy RB