Evolutionary reversion in tumorigenesis

Abstract

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Cells forming malignant tumors are distinguished from those forming normal tissues based on several features: accelerated/dysregulated cell division, disruption of physiologic apoptosis, maturation/differentiation arrest, loss of polarity, and invasive potential. Among them, accelerated cell division and differentiation arrest make tumor cells similar to stem/progenitor cells, and this is why tumorigenesis is often regarded as developmental reversion. Here, in addition to developmental reversion, we propose another insight into tumorigenesis from a phylogeny viewpoint. Based on the finding that tumor cells also share some features with unicellular organisms, we propose that tumorigenesis can be regarded as “evolutionary reversion”. Recent advances in sequencing technologies and the ability to identify gene homologous have made it possible to perform comprehensive cross-species transcriptome comparisons and, in our recent study, we found that leukemic cells resulting from a polycomb dysfunction transcriptionally resemble unicellular organisms. Analyzing tumorigenesis from the viewpoint of phylogeny should reveal new aspects of tumorigenesis in the near future, and contribute to overcoming malignant tumors by developing new therapies.

Keywords

• tumorigenesis
• evolution
• unicellular organism
• multicellularization
• cross-species comparison
• transcriptome