The reverse evolution from multicellularity to unicellularity during carcinogenesis

Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias.

Section: General Characteristics Of Various Kinds Of Cancers Are Uncomentioning

confidence: 76%

Section: General Characteristics Of Various Kinds Of Cancers Are Uncomentioning

confidence: 95%

Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii

Lun

Lai

Wen

et al. 2015

“…Another question is the role that cancer plays in development (25) and the transition from unicellular to multicellular behavior, and the role that cancer has played as an evolutionary variable (33). Because we show that up-expressed nonsubstituted genes and highly substituted genes are predominantly ancient genes, perhaps cancer represents a return to unicellularity that is represented by these crucial and ancient genes, with cancer allowing substitutions in, or abandoning higher-level genes associated with, multicellular cooperation (34). Clearly, with our limited data set, in this paper, we cannot address this question in a deeply quantitative way, but we hope we can point to different ways of viewing how cancer has influenced the process of development and its possible ancient origins.…”

Section: Discussionmentioning

confidence: 92%

Ancient hot and cold genes and chemotherapy resistance emergence

Zhang

Lambert

et al. 2015

We use a microfabricated ecology with a doxorubicin gradient and population fragmentation to produce a strong Darwinian selective pressure that drives forward the rapid emergence of doxorubicin resistance in multiple myeloma (MM) cancer cells. RNA sequencing of the resistant cells was used to examine (i) emergence of genes with high de novo substitution densities (i.e., hot genes) and (ii) genes never substituted (i.e., cold genes). The set of cold genes, which were 21% of the genes sequenced, were further winnowed down by examining excess expression levels. Both the most highly substituted genes and the most highly expressed never-substituted genes were biased in age toward the most ancient of genes. This would support the model that cancer represents a revision back to ancient forms of life adapted to high fitness under extreme stress, and suggests that these ancient genes may be targets for cancer therapy.cancer | emergence | ancient genes | cold | hot

“…It has been reported that disruption of genes tied to multicellularity confers advantages to malignant tumor clones (12), the expression of highly conserved genes is a feature of drug resistance in tumor cells (7), and there is global convergent activation in tumors of transcriptional programs associated with dedifferentiation (12,13). These findings suggest deeper understanding of the differences in the expression and regulation of ancient unicellular and more recently evolved multicellular gene sets during malignant transformation will be crucial for uncovering the molecular basis of common tumor phenotypes and will provide new targets and strategies for cancer therapy.…”

mentioning

confidence: 99%

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

Trigos

Pearson

Papenfuss

et al. 2017

176

217

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.