Louka Aikaterini, Takan Işıl, Pavlopoulou Athanasia, Georgakilas Alexandros G
DNA Damage Laboratory, Department of Physics, School of Applied Mathematical and Physical Sciences, Zografou Campus, National Technical University of Athens (NTUA), 15780 Athens, Greece.
Section of Cell Biology and Biophysics, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece.
Front Biosci (Landmark Ed). 2021 Aug 30;26(8):279-311. doi: 10.52586/4944.
: 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. : In the present study, we have employed bioinformatic approaches for the in-depth investigation of twelve atavistic hub genes (, , , , , , , , , , and ), 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. : 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.
癌症是一种在多细胞生物中普遍存在的现象,代表着一种返祖状态,即细胞沿着逆向进化的路径发展,通过干扰人类基因网络的枢纽基因,开启一套古老的、预先存在的适应性工具包。这导致了一种类似于单细胞生命形式的原始细胞表型。
在本研究中,我们采用生物信息学方法深入研究了12个返祖枢纽基因(、、、、、、、、、、和),这些基因在不同类型的癌症中表现出高度紊乱的相互作用,并与转移的形成有关。为此,我们进行了系统发育分析,以揭示这些枢纽基因的进化历史,并在生命之树中追溯癌症的起源。
根据我们的结果,这些基因中的大多数起源于单细胞,其中一些可以追溯到细胞生命本身的出现(返祖理论)。我们的发现表明癌症的进化根源实际上有多深,并且在临床环境中可用于设计新的治疗方法,特别是在克服对抗肿瘤治疗的耐药性方面。