The life cycle of polyploid giant cancer cells and dormancy in cancer: Opportunities for novel therapeutic interventions.
The life cycle of polyploid giant cancer cells and dormancy in cancer: Opportunities for novel therapeutic interventions.
复制标题
多倍体巨细胞的生命周期和癌症的休眠：新型治疗干预措施的机会。
DOI：
10.1016/j.semcancer.2021.10.005
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发表时间：
2022-06
影响因子：
14.5
通讯作者：
Sood, Anil K.
中科院分区：
文献类型：
--
作者：
Liu, Jinsong;Niu, Na;Li, Xiaoran;Zhang, Xudong;Sood, Anil K.
关键词：
最近的数据表明，癌症治疗中的大多数基因毒性药物可导致基因组休克和细胞大小增加，从而导致全基因组复制或倍增、多倍体巨型癌细胞的形成、早期胚胎程序的激活和体细胞的去分化。这一过程是通过巨细胞生命周期实现的，巨细胞生命周期是最近提出的体细胞恶性转化的机制。细胞大小和倍性的增加使细胞能够完全或部分重组基因组并发育成囊胚样结构，类似于在卵裂球阶段胚胎发生中观察到的结构。虽然具有重编程基因组的囊胚样结构可以产生抗性或转移性子细胞或不同谱系的良性细胞，但它们也获得了经历胚胎滞育的能力，胚胎滞育是一种可逆的悬浮胚胎发育状态，其中细胞为了响应环境压力而进入休眠状态以求生存。治疗药物可以激活这种进化上保守的发育程序，当细胞从胚胎滞育中苏醒时，这会导致复发或转移。了解调节巨细胞生命周期不同阶段的关键机制为治疗干预提供了新的机会。
Recent data suggest that most genotoxic agents in cancer therapy can lead to shock of genome and increase in cell size, which leads whole genome duplication or multiplication, formation of polyploid giant cancer cells, activation of an early embryonic program, and dedifferentiation of somatic cells. This process is achieved via the giant cell life cycle, a recently proposed mechanism for malignant transformation of somatic cells. Increase in both cell size and ploidy allows cells to completely or partially restructures the genome and develop into a blastocyst-like structure, similar to that observed in blastomere-stage embryogenesis. Although blastocyst-like structures with reprogrammed genome can generate resistant or metastatic daughter cells or benign cells of different lineages, they also acquired ability to undergo embryonic diapause, a reversible state of suspended embryonic development in which cells enter dormancy for survival in response to environmental stress. Therapeutic agents can activate this evolutionarily conserved developmental program, and when cells awaken from embryonic diapause, this leads to recurrence or metastasis. Understanding of the key mechanisms that regulate the different stages of the giant cell life cycle offers new opportunities for therapeutic intervention.
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影响因子：
11.2
作者：
Barsoum, Ivraym B.;Smallwood, Chelsea A.;Graham, Charles H.
通讯作者：
Graham, Charles H.
影响因子：
--
作者：
Donovan, Prudence;Cato, Kathleen;Harding, Angus
通讯作者：
Harding, Angus
影响因子：
64.8
作者：
Bulut-Karslioglu, Aydan;Biechele, Steffen;Jin, Hu;Macrae, Trisha A.;Hejna, Miroslav;Gertsenstein, Marina;Song, Jun S.;Ramalho-Santos, Miguel
通讯作者：
Ramalho-Santos, Miguel
DOI：
10.1073/pnas.1320198111
发表时间：
2014-03-04
影响因子：
11.1
作者：
Adams, Daniel L.;Martin, Stuart S.;Cristofanilli, Massimo
通讯作者：
Cristofanilli, Massimo
影响因子：
18.2
作者：
Campisi J
通讯作者：
Campisi J