Three steps to the immortality of cancer cells: senescence, polyploidy and self-renewal

Cancer Cell International

Mark S Cragg¹  Jekaterina Erenpreisa² 

[1] Antibody and Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, General Hospital, University of Southampton, Southampton SO16 6YD, UK;Latvian Biomedical Research & Study Centre, Riga LV-1047, Latvia

关键词: Resistance;    Totipotency;    Reprogramming;    Self-renewal;    Polyploidy;    Senescence;    DNA damage;    Tumour cells;   

Others  :  792899
DOI  :  10.1186/1475-2867-13-92

 received in 2013-05-19, accepted in 2013-07-24,  发布年份 2013

【 摘 要 】

Metastatic cancer is rarely cured by current DNA damaging treatments, apparently due to the development of resistance. However, recent data indicates that tumour cells can elicit the opposing processes of senescence and stemness in response to these treatments, the biological significance and molecular regulation of which is currently poorly understood. Although cellular senescence is typically considered a terminal cell fate, it was recently shown to be reversible in a small population of polyploid cancer cells induced after DNA damage. Overcoming genotoxic insults is associated with reversible polyploidy, which itself is associated with the induction of a stemness phenotype, thereby providing a framework linking these separate phenomena. In keeping with this suggestion, senescence and autophagy are clearly intimately involved in the emergence of self-renewal potential in the surviving cells that result from de-polyploidisation. Moreover, subsequent analysis indicates that senescence may paradoxically be actually required to rejuvenate cancer cells after genotoxic treatments. We propose that genotoxic resistance is thereby afforded through a programmed life-cycle-like process which intimately unites senescence, polyploidy and stemness.

【 授权许可】

   
2013 Erenpreisa and Cragg; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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