Cancer across the tree of life: cooperation and cheating in multicellularity

Abstract

Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer.

Innovation: an emerging focus from cells to societies

“…Aktipis & Maley discuss how the tension between cooperation and cheating in multicellular organisms leads to innovations in the host, such as programmed cell death and immune systems that protect against disease from within and disease caused by other organisms. Moreover, innovations may emerge in cellular cheaters, such as invasive neoplasms (cancer), examples including evading the immune system, adapting to and changing the microenvironment, and dispersing to colonize new, hospitable tissues and organs [136]. Similar reasoning applies to visitors or residents in the organism, such as beneficial, neutral or pathogenic species and strains in the microbiota [137].…”

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

“…Genes commonly involved in cancer associate with two major evolutionary events: the emergence of self-replicating cellular life and the appearance of simple multicellular organisms (6,7). The disruption of genes and processes that appeared in early metazoan life to enhance intercellular cooperation is expected to be a recurrent driver of carcinogenesis, as implicated by the widespread occurrence of cancer across the tree of multicellular life (8,9) and the common dysregulation of pathways that evolved to sustain multicellularity, such as Wnt and integrins (10,11).…”

How Research on Microbiomes is Changing Biology: A Discussion on the Concept of the Organism

“…Nevertheless, there may still be some room for the emergence of internal conflict. One example is cancer, which is not limited to cats or animals, but which seems to be a kind of conflict common to all multicellular organisms (see Aktipis et al 2015). Basically, by cancer we mean a situation in which a cell stops performing its normal functions (mainly due to mutations) and starts to reproduce, at an uncontrolled rate, to the detriment of the organism, leading very often to its death.…”