The definition of multicellularity centres on having cells with the capacity to cooperate and organise to form functional tissues. Cancer is the opposite. During carcinogenesis, cancerous cell behaves differently from normal cells by dividing uncontrollably to form lumps of tumour that endangers the integrity of a tissue or organ within a multicellular organism.
Several studies have hypothesised that multicellular life originated from unicellular organisms. There are various theories that further explain how this transition came to be. The colonial theory of multicellular life for example suggests that animal life originated from the colonies of ancient similar unicellular species. Cellular differentiation and cooperation subsequently existed within this colony before gradually evolving into a single multicellular organism.
Cancer seems to be a reversal of multicellularity. There are in fact several scientific studies and reviews that explore and compare the association between the biological functions and operational definitions of multicellularity and cancer.
In addition, it also important to remember that cancers are caused by faulty genes, particularly by mutations in two classes of genes called the proto-oncogenes that are responsible for regulating cell growth and tumour suppressor genes that are responsible for slowing down cellular division rate and programming cellular lifespan.
Researchers H. Chen, F. Lin, K. Xing, and S. He described carcinogenesis as the reverse evolution from multicellularity to unicellularity. They studied the whole-life history of a xenograft tumour and demonstrated how positive selection for general loss-of-function mutations on multicellularity-related genes drive metastasis or the spread of cancer from one organ to another.
Expression analyses further revealed downregulation of multicellularity-related genes and an evolving expression profile leaning toward that of an embryotic stem cells. Take note that an embryotic stem cells resembles unicellular life because it also have the capacity of unlimited clonal proliferation.
An elevated birth rate of cancer genes has been associated with the emergence of animal life about 600 million years ago. The study also found that a typical tumour has more loss-of-function tumour suppressors than activated oncogenes.
Based from the aforementioned findings, the study concluded that cancer represents a loss-of-function-driven reverse evolution back to the unicellular.
A review study by C. A. Aktipis et al involving literatures on cancer and cancer-like phenomenon concluded that the characterisation of cancer centres on the breakdown of critical features of cooperation that characterises multicellularity. These features include cheating in proliferation inhibition, cell death, division of labour, resource allocation, and extracellular environment maintenance. A cancerous cell essentially behaves delinquently from the rest.
Cheating is central to cancer and carcinogenesis. The researchers noted that cooperation is at the heart of multicellularity. This cooperation is critical for the development, maintenance, and reproduction of a multicellular organism. A cancerous cell essentially cheats within this cooperative multicellular system.
The aforementioned study also concluded that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis. This might be underappreciated in studies involving cancers.
Another study by P. C. W. Davies and C. Lineweaver mentioned that genes of cellular cooperation that evolved with multicellularity about a billion years ago are the same genes that malfunction to cause cancer.
The study provides a hypothesis that cancer or carcinogenesis is an atavistic condition occurring when a genetic or epigenetic malfunction unlocks an ancient toolkit or mechanism involving pre-existing adaptations. This unlocking re-establishes the dominance of an earlier layer of genes that controlled loose-knit colonies of only partially differentiated cells, similar to tumors.
Because the mechanism responsible for turning a healthy cell into a cancerous cell has been existing before and during the early days of multicellular animal life, Davies and Lineweaver further noted that cancer s not a newly evolved biological conditions. Cancer cells are heirs to an ancient toolkit and a basic mode of survival that is deeply embedded in multicellular life.
Virtually every healthy multicellular animals have cancer mechanisms or pathways that remain active. Examples of these are those used in embryogenesis and wound healing. Other pathways remain dormant within the genome, awaiting activation.
Cancers and tumors can easily be regarded as a type of living fossil from the era when the first generation of animal life emerged and lived. Multicellularity and cancer seem inseparable conditions based on this starling atavism hypothesis of Davies and Lineweaver.
There is undeniably an interesting association between multicellularity and cancer. The referenced studies describe multicellularity as a condition characterised by the emergence of cell differentiation while maintaining cooperation needed to form and maintain tissues with varying functions within a multicellular system. The biological integrity of a multicellular organism remains intact due to cooperation.
Cancer is the opposite condition of multicellularity. The separate studies suggest that cancer is a reverse evolution from multicellularity to unicellularity. They also describe cancer as a loss of multicellularity.
Multicellularity and cancer thereby seem to be inevitably associated. Cooperation among cells lead to multicellular system but the absence of this cooperation promotes carcinogenesis and tumour growth that lead to the development of cancer.
The key takeaways from exploring the association between multicellularity and cancer centre on advancing current understanding about the nature of cancer that could lead to identification of possible therapies. Davies and Lineweaver for instance suggested that instead of attacking tumours indiscriminately, understanding their origin, managing them and containing them might be a far better strategy. Chen et al suggests that their model might account for intertumoural or intratumoural genetic heterogeneity that could explain distant-organ metastases and hold implications for cancer therapy.
Further details of the study of Chen et al are in the article “The reverse evolution from multicellularity to unicellularity during carcinogenesis” published in 2015 in the journal Nature Communication. More details of the study of C. A. Aktipis et al are in the article “Cancer across the tree of life: Cooperation and cheating in multicellularity” published in 2015 in the journal Philosophical Transactions of the Royal Society of London. Further details of the study of Davies and Lineweaver are in the article “Cancer tumors as metazoa 1.0: Tapping genes of ancient ancestors” published in 2011 in the journal Physical Biology.