Circadian clock protein CRY1 prevents paclitaxelinduced senescence of bladder cancer cells by promoting p53 degradation.
Oncol Rep
; 45(3): 1033-1043, 2021 03.
Article
en En
| MEDLINE
| ID: mdl-33650658
ABSTRACT
Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The firstline treatment is cisplatinbased combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapyinduced senescence can act as a 'backup' response to chemotherapy in cancer types that are resistant to apoptosisbased anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)induced senescence in cisplatinresistant bladder cancer cells. Cisplatinresistant bladder cancer cells were established via longterm cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SAßGal staining, but this was not observed in the cisplatinresistant cells. The cisplatinresistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatinresistant cells, and that CRY1 knockdown restored PTXinduced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 protooncogene. These data suggested that the accumulated CRY1 in cisplatinresistant cells could prevent PTXinduced senescence by promoting p53 degradation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
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Proteína p53 Supresora de Tumor
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Senescencia Celular
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Paclitaxel
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Criptocromos
Límite:
Humans
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2021
Tipo del documento:
Article