ROS-induced cell cycle arrest as a mechanism of resistance in polyaneuploid cancer cells (PACCs).

ROS-induced cell cycle arrest as a mechanism of resistance in polyaneuploid cancer cells (PACCs).
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DOI:
10.1016/j.pbiomolbio.2021.05.002
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发表时间:
2021-10
影响因子:
3.8
通讯作者:
Amend SR
Amend SR
中科院分区:
生物学3区
文献类型:
--
作者:
Kuczler MD;Olseen AM;Pienta KJ;Amend SR

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癌症每年导致全世界数百万人死亡。一旦转移,这种疾病是不可治愈的,并显示出对所有抗癌疗法的抵抗力。癌细胞中已经升高的活性氧(ROS)水平通过治疗进一步增加。氧化应激激活DNA损伤反应(DDR),并且应激的癌细胞朝向细胞周期停滞移动。一旦被阻止,大多数癌细胞将以凋亡的形式进行程序性细胞死亡。如果癌细胞能够在细胞分裂之前退出细胞周期并进入受保护的G0状态,则其能够作为多非整倍体癌细胞(PACC)耐受治疗并存活,并最终产生耐药性肿瘤生长。
Cancer is responsible for the deaths of millions of people worldwide each year. Once metastasized, the disease is incurable and shows resistance to all anti-cancer therapies. The already-elevated level of reactive oxygen species (ROS) in cancer cells is further increased by therapies. The oxidative stress activates the DNA damage response (DDR) and the stressed cancer cell moves towards cell cycle arrest. Once arrested, the majority of cancer cells will undergo programmed cell death in the form of apoptosis. If the cancer cell is able to exit the cell cycle prior to cell division and enter a protected G0 state, it is able to withstand and survive therapy as a polyaneuploid cancer cell (PACC) and eventually seed resistant tumor growth.
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