Unit:
Κατεύθυνση ΒιοπληροφορικήLibrary of the School of Science
Supervisors info:
Αλέξανδρος Γεωργακίλας, Αναπληρωτής Καθηγητής, Σ.Ε.Μ.Φ.Ε., Εθνικό Μετσόβειο Πολυτεχνείο
Ιωάννης Τρουγκάκος, Καθηγητής, Τμήμα Βιολογίας, Πανεπιστήμιο Αθηνών
Παντελής Μπάγκος, Καθηγητής, Τμήμα Πληροφορικής με Εφαρμογές στη Βιοϊατρική, Πανεπιστήμιο Θεσσαλίας
Original Title:
Φυλογενετική ανάλυση αταβιστικών γονιδίων που σχετίζονται με διάφορες μορφές καρκίνου.
Translated title:
Phylogenetic analysis of atavistic genes associated with various cancer types.
Summary:
Cancer and cancel-like phenomena have been observed in almost all species that exhibit either clonal or aggregative multicellularity. In fact, each one of the hallmarks of cancer is a direct violation of the principles of multicellular cooperation. Cancer represents a disruption of the complex molecular and cellular mechanisms, which enable multicellular cooperation by imposing constraints on cell growth and the result is a more primitive cellular phenotype resembling a unicellular life form. During carcinogenesis, cells follow a path of reverse evolution by disrupting the coordination of multicellular and unicellular processes and depending heavily on the latter. This is achieved by disrupting certain genes that connect the two subnetworks of the human genes network, one of unicellular origin and the other of multicellular origin with the latter having been built upon the first one through years of evolution to enable multicellular cooperation. This phenomenon of mutual exclusivity occurs through the disruption of certain hub genes which connect the two subnetworks. Thus, cancer cells behave as primitive unicellular organisms whose functions and characteristics are encoded within the genes of the healthy cell and just a few changes are enough to bring this living fossil that lies dormant within every cell to the surface. According to the atavistic model of cancer, cancer cells display some unicellular behavior.
In the present study, we investigated certain genes which have previously been proven to exhibit highly disrupted interactions in many types of cancer and contribute to the phenomenon of mutual exclusivity. Each gene has been associated with multiple types of cancer in different tissues and are considered as biomarkers or drug targets for these types of cancer. More precisely, all those genes are associated with cancer’s most dangerous characteristic, the formation of metastasis. Furthermore, each gene participates in at least one of the paths and cellular processes which are associated with cancer. Consequentially, since the origin of cancer is believed to be found in the early transitional phase from unicellular to early multicellular life forms, long before the emergence of complex Metazoans, we conducted phylogenetic analysis of the aforementioned genes by following the lineage of humans. Certain of those genes were present solely in Metazoans while others were present solely on Eukaryotes and some have occurred in a catholic common ancestor of Eukaryotes, Prokaryotes and Archaea. Therefore, the genes that play a crucial role in carcinogenesis and metastasis have deep evolutionary roots, since they appeared long before the emergence of Metazoa and some of them can be traced back to the emergence of life itself billions of years ago.
Those findings have important implications on therapeutic strategies, since certain genes and their products as well as the functions and paths in which they participate, can be considered as pancancer biomarkers and drug targets for a wide variety of cancer types. In general, the application of evolutionary principles and analysis in the field of comparative oncology can lead to a deeper understanding of cancer as a phenomenon that is inextricably linked with multicellularity and provide novel therapeutic approaches for the cure of an ancient disease.
Main subject category:
Science
Keywords:
atavistic model, cancer, genes, evolution, phylogenetic analysis
Number of references:
417
