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Stress-induced polyploidy shifts somatic cells towards a pro-tumourogenic unicellular gene transcription networkстатья
- Авторы: Erenpreisa J., Giuliani A., Vinogradov A.E., Anatskaya O.V., Vazquez-Martin A., Salmina K., Cragg M.S.
- Журнал: Cancer Hypotheses
- Том: 1
- Номер: 1
- Год издания: 2018
- Первая страница: 1
- Последняя страница: 20
- Аннотация: Theories of cancer are central to our understanding of biology and receive frequent refinement. Here, we propose a link between key aspects of the atavistic theory of cancer and the capacity of polyploidy to access transcriptional networks of unicellular organisms. Polyploid cells are known to display greater capacity for adaptation to environmental challenge than their diploid counterparts. Whole genome duplication (WGD) induced by environmental crisis is crucial for facilitating the genetic bias of speciation and for providing the long-term increase in genetic and biological complexity. Somatic tumour cells appear to reverse this process in response to stress. Our recent studies reveal that polyploidy is cooperatively linked by cellular stress to stemness, dedifferentiation and a shift towards the transcriptional networks typical of unicellular organisms. We hypothesise that when cells undergo polyploidy they enter a transcriptional continuum enabling rapid epigenetic adaptation to environmental challenge followed by clonal selection of genetic differences. For tumour cells, in the absence of tumour suppressors this polyploidy-induced stemness state provides access to the transcriptional network of eukaryotic precursors, whose immortality and survival fitness are supported by their a-sexual ploidy life cycles. This process can be equated to a reversal along the phylogenetic tree of evolution providing the single-cell autonomy and immortality that are fundamental hallmarks of cancer.
- Добавил в систему: Виноградов Александр Евгеньевич