Circadian clock protein CRY1 prevents paclitaxel‑induced senescence of bladder cancer cells by promoting p53 degradation.
Circadian clock protein CRY1 prevents paclitaxel‑induced senescence of bladder cancer cells by promoting p53 degradation.
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昼夜节律钟蛋白E11通过促进p53降解防止紫杉醇诱导的膀胱癌细胞衰老。
DOI：
10.3892/or.2020.7914
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发表时间：
2021-03
期刊：
影响因子：
4.2
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Jia M;Su B;Mo L;Qiu W;Ying J;Lin P;Yang B;Li D;Wang D;Xu L;Li H;Zhou Z;Li X;Li J
膀胱癌是泌尿系统常见的肿瘤类型，具有较高的发病率和死亡率。一线治疗是以顺铂为基础的联合化疗，但很大一部分患者由于耐药性的产生而复发。对于对基于细胞凋亡的抗癌疗法有抵抗力的癌症类型，治疗诱导的衰老可以作为化疗的“备用”反应。生物钟在耐药性和细胞衰老中发挥着重要作用。本研究的目的是探讨生物钟对紫杉醇（PTX）诱导的顺铂耐药膀胱癌细胞衰老的调节作用。通过长期顺铂孵育建立顺铂耐药性膀胱癌细胞。通过 SA-β-Gal 染色证明，PTX 诱导膀胱癌细胞明显衰老，但在顺铂耐药细胞中未观察到这一现象。顺铂耐药细胞在急性 PTX 应激下进入休眠状态，昼夜节律延长。研究发现，昼夜节律蛋白 Cryptochrome1 (CRY1) 在这些静止的顺铂耐药细胞中积累，并且 CRY1 敲低可恢复 PTX 诱导的衰老。从机制上讲，CRY1 通过增加 p53 与其泛素 E3 连接酶 MDM2 原癌基因的结合来促进 p53 降解。这些数据表明，顺铂耐药细胞中积累的 CRY1 可以通过促进 p53 降解来防止 PTX 诱导的衰老。
Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first-line treatment is cisplatin-based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy-induced senescence can act as a ‘back-up’ response to chemotherapy in cancer types that are resistant to apoptosis-based 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 cisplatin-resistant bladder cancer cells. Cisplatin-resistant bladder cancer cells were established via long-term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA-β-Gal staining, but this was not observed in the cisplatin-resistant cells. The cisplatin-resistant 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 cisplatin-resistant cells, and that CRY1 knockdown restored PTX-induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto-oncogene. These data suggested that the accumulated CRY1 in cisplatin-resistant cells could prevent PTX-induced senescence by promoting p53 degradation.
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影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
4.3
作者：
Antoch, Marina P.;Gorbacheva, Victoria Y.;Nikitin, Alexander Yu
通讯作者：
Nikitin, Alexander Yu
夜间暴露在光线下造成的昼夜节律和褪黑激素的破坏会导致乳腺癌对他莫昔芬治疗产生内在耐药性。
影响因子：
11.2
作者：
Dauchy RT;Xiang S;Mao L;Brimer S;Wren MA;Yuan L;Anbalagan M;Hauch A;Frasch T;Rowan BG;Blask DE;Hill SM
通讯作者：
Hill SM
影响因子：
6.2
作者：
Kavanagh EL;Lindsay S;Halasz M;Gubbins LC;Weiner-Gorzel K;Guang MHZ;McGoldrick A;Collins E;Henry M;Blanco-Fernández A;O Gorman P;Fitzpatrick P;Higgins MJ;Dowling P;McCann A
通讯作者：
McCann A
影响因子：
64.8
作者：
Lamia, Katja A.;Papp, Stephanie J.;Yu, Ruth T.;Barish, Grant D.;Uhlenhaut, N. Henriette;Jonker, Johan W.;Downes, Michael;Evans, Ronald M.
通讯作者：
Evans, Ronald M.