IMR Press / FBL / Volume 26 / Issue 8 / DOI: 10.52586/4944
Open Access Original Research
Bioinformatic approaches to the investigation of the atavistic genes implicated in cancer
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1 DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, Zografou Campus, National Technical University of Athens (NTUA), 15780 Athens, Greece
2 Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece
3 Izmir Biomedicine and Genome Center (IBG), 35340 Balcova, Izmir, Turkey
4 Izmir International Biomedicine and Genome Institute, Genomics and Molecular Biotechnology Department, Dokuz Eylül University, 35340 Balcova, Izmir, Turkey
*Correspondence: (Athanasia Pavlopoulou); (Alexandros G. Georgakilas)
Front. Biosci. (Landmark Ed) 2021, 26(8), 279–311;
Submitted: 7 June 2021 | Revised: 19 July 2021 | Accepted: 30 July 2021 | Published: 30 August 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (

Introduction: Cancer is a widespread phenomenon occurring across multicellular organisms and represents a condition of atavism, wherein cells follow a path of reverse evolution that unlocks a toolkit of ancient pre-existing adaptations by disturbing hub genes of the human gene network. This results to a primitive cellular phenotype which resembles a unicellular life form. Methods: In the present study, we have employed bioinformatic approaches for the in-depth investigation of twelve atavistic hub genes (ACTG1, CTNNA1, CTNND1, CTTN, DSP, ILK, PKN2, PKP3, PLEC, RCC2, TLN1 and VASP), which exhibit highly disrupted interactions in diverse types of cancer and are associated with the formation of metastasis. To this end, phylogenetic analyses were conducted towards unravelling the evolutionary history of those hubs and tracing the origin of cancer in the Tree of Life. Results: Based on our results, most of those genes are of unicellular origin, and some of them can be traced back to the emergence of cellular life itself (atavistic theory). Our findings indicate how deep the evolutionary roots of cancer actually are, and may be exploited in the clinical setting for the design of novel therapeutic approaches and, particularly, in overcoming resistance to antineoplastic treatment.

Biological pathways
Fig. 1.
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