Prolonged autophagy by MTOR inhibitor leads radioresistant cancer cells into senescence

Title
Prolonged autophagy by MTOR inhibitor leads radioresistant cancer cells into senescence
Authors
Hae Yun NamMyung Woul HanHyo Won Chang김상윤Seong Who Kim
Keywords
MTOR inhibitor; irradiation; cellular senescence; autophagy; RB
Issue Date
2013-10
Publisher
Autophagy
Citation
VOL 9, NO 10, 1631-1632
Abstract
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 (β-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 autophagysurvival mode to radiotherapy.
URI
http://pubs.kist.re.kr/handle/201004/46264
ISSN
15548627
Appears in Collections:
KIST Publication > Article
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