Salmina, K.; Pjanova, A.; Huna, M.; Kalejs, D.; Scherthan, H.; Cragg, M.S.; Erenpreisa, J. The Cancer Aneuploidy Paradox: In the Light of Evolution. Genes2019, 10, 83.
Salmina, K.; Pjanova, A.; Huna, M.; Kalejs, D.; Scherthan, H.; Cragg, M.S.; Erenpreisa, J. The Cancer Aneuploidy Paradox: In the Light of Evolution. Genes 2019, 10, 83.
Salmina, K.; Pjanova, A.; Huna, M.; Kalejs, D.; Scherthan, H.; Cragg, M.S.; Erenpreisa, J. The Cancer Aneuploidy Paradox: In the Light of Evolution. Genes2019, 10, 83.
Salmina, K.; Pjanova, A.; Huna, M.; Kalejs, D.; Scherthan, H.; Cragg, M.S.; Erenpreisa, J. The Cancer Aneuploidy Paradox: In the Light of Evolution. Genes 2019, 10, 83.
Abstract
Aneuploidy should compromise cellular proliferation but paradoxically favours tumour progression and poor prognosis. Here, we consider this paradox in terms of our most recent observations of chemo/radio-resistant cells undergoing reversible polyploidy. The latter perform segregation of two parental groups of end-to-end linked dyads by pseudo-mitosis creating tetraploid cells through a dysfunctional spindle. This is followed by autokaryogamy and homologous pairing preceding a bi-looped endo-prophase. The associated RAD51 and DMC1/γ-H2AX double-strand break repair foci are tandemly situated on the AURKB/REC8/kinetochore doublets along replicated chromosome loops, indicative of recombination events. MOS-associated REC8-positive peri-nucleolar centromere cluster organises a monopolar spindle. The process is completed by reduction divisions (bi-polar or with radial cytotomy including pedogamic exchanges) and release of secondary cells and/or formation of an embryoid. Together this process preserves genomic integrity and chromosome pairing, while tolerating aneuploidy by by-passing the mitotic spindle and meiotic SC checkpoints. Concurrently, it reduces the chromosome number and facilitates recombination that decreases the mutation load of aneuploidy and lethality in the chemo-resistant tumour cells. This cancer life-cycle has parallels both within the cycling polyploidy of the asexual life cycles of ancient unicellular protists and cleavage embryos of early multicellulars, supporting the atavistic theory of cancer.
Biology and Life Sciences, Cell and Developmental Biology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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