The Transcriptome and Proteome Networks of Malignant Tumours Reveal Atavistic Attractors of Polyploidy-Related Asexual Reproduction

Abstract

The expression of gametogenesis-related (GG) genes and proteins, as well as whole genome duplications (WGD), are the hallmarks of cancer related to poor prognosis. Currently, it is not clear if these hallmarks are random processes associated only with genome instability or are programmatically linked. Our goal was to elucidate this via a thorough bioinformatics analysis of 1474 GG genes in the context of WGD. We examined their association in protein–protein interaction and coexpression networks, and their phylostratigraphic profiles from publicly available patient tumour data. The results show that GG genes are upregulated in most WGD-enriched somatic cancers at the transcriptome level and reveal robust GG gene expression at the protein level, as well as the ability to associate into correlation networks and enrich the reproductive modules. GG gene phylostratigraphy displayed in WGD+ cancers an attractor of early eukaryotic origin for DNA recombination and meiosis, and one relative to oocyte maturation and embryogenesis from early multicellular organisms. The upregulation of cancer–testis genes emerging with mammalian placentation was also associated with WGD. In general, the results suggest the role of polyploidy for soma–germ transition accessing latent cancer attractors in the human genome network, which appear as pre-formed along the whole Evolution of Life.

Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model

“…Among the most strongly upregulated GO processes in polyploid vs. diploid cancer cells is the ‘female meiotic nuclear division’. This observation confirms previous reports on the activation of meiotic genes in polyploid cancer cells [ 95 , 96 , 97 , 98 ]. This fact can be a sign of genetic recombination, which is reminiscent of sexual generations arising in apomictic (clonal) animal and plant populations under stressful conditions and may be inherited from the evolutionary past.…”

The Role of Mitotic Slippage in Creating a “Female Pregnancy-like System” in a Single Polyploid Giant Cancer Cell

“…Because of renewed interest in the atavistic theory of cancer [ 16 ], and an understanding of how cancer attractors during evolution are associated with polyploidy related to asexual reproduction, as recently identified in the TCGA database, including for breast carcinoma [ 17 ], we were interested in if and how these differences in gene expression changed the phylostratigraphic gene profiles.…”

“…Therefore it is interesting that recently we revealed oocyte maturation and meiotic cell division in the STRING PPI network of the TCGA database BRCA (and some other cancers) patient sample cohort in association with whole genome duplications [ 17 ]. So, the current in silico and immunofluorescence data in our MDA-MB-231-DOX model confirm the reality of such cell-fate change of somatic cancer cells.…”

Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats

“…Beyond the association between NLI and the well-established features of heart pathology in the main signaling pathways, our data also revealed the morphologic and transcriptomic traits of increased polyploidy that are also known to accompany various heart diseases, including tetralogy of Fallot, cardiomyopathy, hypertension, and ischemic heart disease [ 14 , 51 , 89 , 129 , 130 , 131 ]. Among these features are the response to DNA and telomere damage and the impairment of circadian entrainment [ 73 , 132 , 133 , 134 ]. Our data also uncovered ploidy-related manifestations of the fetal phenotype in the signaling pathways and metabolism [ 88 , 135 , 136 , 137 ].…”