Please use this identifier to cite or link to this item:
10.3390/genes10020083
Title: | The cancer aneuploidy paradox : In the light of evolution |
Authors: | Salmina, Kristine Huna, Anda Kalejs, Martins Pjanova, Dace Scherthan, Harry Cragg, Mark S. Erenpreisa, Jekaterina Scientific Laboratory of Biomechanics |
Keywords: | Aneuploidy;Autokaryogamy;Cancer;Chromothripsis;Cleavage embryo;Disabled spindle;Meio-mitosis;Recombination on kinetochores;Reduction;Somatic pairing;3.1 Basic medicine;3.2 Clinical medicine;1.1. Scientific article indexed in Web of Science and/or Scopus database;Genetics;Genetics(clinical);SDG 3 - Good Health and Well-being |
Issue Date: | 1-Jan-2019 |
Citation: | Salmina , K , Huna , A , Kalejs , M , Pjanova , D , Scherthan , H , Cragg , M S & Erenpreisa , J 2019 , ' The cancer aneuploidy paradox : In the light of evolution ' , Genes , vol. 10 , no. 2 , 83 . https://doi.org/10.3390/genes10020083 |
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 the 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 a 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 by radial cytotomy including pedogamic exchanges) and by the release of secondary cells and/or the formation of an embryoid. Together this process preserves genomic integrity and chromosome pairing, while tolerating aneuploidy by by-passing the mitotic spindle checkpoint. 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. |
Description: | Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2019 Elsevier B.V., All rights reserved. |
DOI: | 10.3390/genes10020083 |
ISSN: | 2073-4425 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
Files in This Item:
File | Size | Format | |
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The_Cancer_Aneuploidy_Paradox.pdf | 4.57 MB | Adobe PDF | View/Open |
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