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首页> 外文期刊>Cell biology international. >Polyploid tumour cells elicit paradiploid progeny through depolyploidizing divisions and regulated autophagic degradation.
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Polyploid tumour cells elicit paradiploid progeny through depolyploidizing divisions and regulated autophagic degradation.

机译：多倍体肿瘤细胞通过去多倍体化分裂和调节自噬降解来引发二倍体后代。

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'Neosis' describes the process whereby p53 function-deficient tumour cells undergo self-renewal after genotoxic damage apparently via senescing ETCs (endopolyploid tumour cells). We previously reported that autophagic digestion and extrusion of DNA occurs in ETC and subsequently revealed that self-renewal transcription factors are also activated under these conditions. Here, we further studied this phenomenon in a range of cell lines after genotoxic damage induced by gamma irradiation, ETO (etoposide) or PXT (paclitaxel) treatment. These experiments revealed that chromatin degradation by autophagy was compatible with continuing mitotic activity in ETC. While the actively polyploidizing primary ETC produced early after genotoxic insult activated self-renewal factors throughout the polygenome, the secondary ETC restored after failed multipolar mitosis underwent subnuclei differentiation. As such, only a subset of subnuclei continued to express OCT4 and NANOG, while those lacking these factors stopped DNA replication and underwent degradation and elimination through autophagy. The surviving subnuclei sequestered nascent cytoplasm to form subcells, while being retained within the confines of the old ETC. Finally, the preformed paradiploid subcells became released from their linking chromosome bridges through autophagy and subsequently began cell divisions. These data show that 'neotic' ETC resulting from genotoxically damaged p53 function-deficient tumour cells develop through a heteronuclear system differentiating the polyploid genome into rejuvenated 'viable' subcells (which provide mitotically propagating paradiploid descendents) and subnuclei, which become degraded and eliminated by autophagy. The whole process reduces aneuploidy in descendants of ETC.
机译：“ Neosis”描述了过程，在此过程中，p53功能缺陷的肿瘤细胞在明显的遗传毒性损伤后会通过感觉敏锐的ETC（内多倍体肿瘤细胞）进行自我更新。我们以前报道过，ETC中发生了DNA的自噬消化和挤出，随后揭示了在这些条件下也激活了自我更新的转录因子。在这里，我们进一步研究了在γ射线，ETO（依托泊苷）或PXT（紫杉醇）治疗引起的遗传毒性损伤后一系列细胞系中的这种现象。这些实验表明，自噬导致的染色质降解与ETC中持续的有丝分裂活性兼容。遗传毒性侵害激活了整个多基因组中的自我更新因子后，就产生了主动多倍化的初级ETC，而在多极有丝分裂失败后进行亚核分化后，二级ETC得以恢复。因此，只有亚核的一个子集继续表达OCT4和NANOG，而缺少这些因子的那些则停止DNA复制，并通过自噬进行降解和消除。幸存的亚核将新生的细胞质隔离形成亚细胞，同时保留在旧的ETC范围内。最后，预先形成的二倍体亚细胞通过自噬从连接的染色体桥中释放出来，随后开始细胞分裂。这些数据表明，由于基因毒性受损的p53功能缺陷的肿瘤细胞而产生的“ neotic” ETC是通过异核系统发育而来的，该系统将多倍体基因组分化为恢复活力的“存活”亚细胞（提供有丝分裂繁殖的二倍体后代）和亚核，这些亚细胞被降解并消除了。自噬。整个过程减少了ETC后代的非整倍性。

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