The evolution of multicellularity and cancer: views and paradigms

Abstract

Conceptually and mechanistically, the evolution of multicellularity required the integration of single cells into new functionally, reproductively and evolutionary stable multicellular individuals. As part of this process, a change in levels of selection occurred, with selection at the multicellular level overriding selection at the cell level. The stability of multicellular individuals is dependent on a combination of mechanisms that supress within-group evolution, by both reducing the occurrence of somatic mutations as well as supressing somatic selection. Nevertheless, mutations that, in a particular microenvironment, confer mutant lineages a fitness advantage relative to normal somatic cells do occur, and can result in cancer. This minireview highlights several views and paradigms that relate the evolution of multicellularity to cancer. As a phenomenon, cancer is generally understood as a failure of multicellular systems to suppress somatic evolution. However, as a disease, cancer is interpreted in different frameworks: (i) a breakdown of cooperative behaviors underlying the evolution of multicellularity, (ii) a disruption of molecular networks established during the emergence of multicellularity to impose constraints on single-celled units, or (iii) an atavistic state resulting from reactivating primitive programs that originated in the earliest unicellular species. A number of assumptions are common in all the views relating cancer as a disease to the evolution of multicellularity. For instance, cancer is considered a reversal to unicellularity, and cancer cells are thought to both resemble unicellular organisms and benefit from ancestral-like traits. Nevertheless, potential limitations of current paradigms should be acknowledged as different perspectives can provide novel insights with potential therapeutic implications.

Keywords: cancer; cheater; evolution of multicellularity; paradigm; tumor suppressors; unicellular.