Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors

Davies, Paul; Lineweaver, Charles H.

doi:10.1088/1478-3975/8/1/015001

Cited by 215 publications

(214 citation statements)

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“…We investigated the biological processes included under the stress response GO term, a broad and varied category highly relevant to tumor biology thought to be central to the atavistic process in cancer (2,3,22). We found 55% of stress responses conserved with unicellular species were up-regulated in tumors, whereas 69% of stress responses exclusive to multicellular organisms were down-regulated (Fig.…”

Section: The Activation Of Response To Stress Mechanisms In Tumors Ismentioning

confidence: 99%

“…Cancer has been suggested to result from an atavistic process, whereby the activation of primitive, highly conserved programs (2,3) leads to molecular phenotypes and population dynamics (4) similar to those of unicellular organisms (5). 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).…”

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confidence: 99%

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

Trigos

Pearson

Papenfuss

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

176

217

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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.

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Section: The Activation Of Response To Stress Mechanisms In Tumors Ismentioning

confidence: 99%

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

Proc. Natl. Acad. Sci. U.S.A.

176

217

View full text Add to dashboard Cite

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“…Several investigators have spoken of cancer as an atavism to an earlier evolutionary state [Davies and Lineweaver, 2011;Davila and Zamorano, 2013] or as a new species [Knauss and Klein, 2012;Vincent, 2010]. Van Valen [1991] referred to cells from the cervical cancer of Henriette Lacks [sic, Henrietta Lacks, see Skloot, 2010] as the species Helacyton gartleri belonging to the family Helacytidae.…”

Section: Appendix: Cancer An Atavism?mentioning

confidence: 99%

“…Domazet-Lošo and Tautz [2010] found two strong peaks of emergence of cancer-related protein domains-one at the time of origin of the first cell and another at the time of evolution of metazoans corresponding respectively to the caretakers and the gatekeepers. Hartl et al [2010] find stem-cell specific activation of the c-myc proto-oncogene in Hydra, a cnidarian and sister group to the eumetazoa, suggesting that the principal function of the "myc master regulator arose very early in the metazoan evolution" (some 600 MYA [Davies and Lineweaver, 2011]), "showing, in Hydra, regenerative ability but no senescence" Hartl et al [2010]. Srivastava et al [2010], sequencing the demosponge Amphimedon queenslandica, found the Myc protein present in other animals, with intact 4-amino acid N-terminal DCMW motif which is lacking in Monosiga brevicollis (a choanoflagellate, King et al [2008], Nielsen [2012], now referred to as a choanomastigote, Margulis and Chapman, [2010]).…”

Section: Appendix: Cancer An Atavism?mentioning

confidence: 99%

“…According to Hartl et al [2010] the protein product Myc of the cellular c-myc proto-oncogene is the central part of a cellular transcription regulator network controlling expression of about 15% of all human genes involved in cell growth, proliferation, differentiation, metabolism, and apoptosis, and that deregulation of c-myc gene with increased levels of myc occurs in about 30% of all human cancers. Davies and Lineweaver [2011] consider cancer an "atavistic condition" due to genetic/epigenetic malfunction that "unlocks" (derepresses) an $1 BY-old ancient "tool kit" of pre-existing adaptations, re-establishing dominance of an earlier layer of genes that controlled loose-knit colonies of partially differentiated cells -"similar to tumors," cancer then being an actual or potential burden of all metazoans in whom adult cells proliferate, except perhaps for the naked mole rat [Suluanov et al, 2009].…”

Section: Appendix: Cancer An Atavism?mentioning

confidence: 99%

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Annals of morphology. Atavisms: Phylogenetic lazarus?

Zanni

Opitz

2013

American J of Med Genetics Pt A

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Dedication: with highest respect and affection to Prof. Giovanni Neri on the eve of his official administrative retirement as Chair of the Institute of Medical Genetics of the Università Cattolica of Rome for leadership in medical genetics and medical science and friendship for decades. The concept “atavism,” reversion, throwback, Rückschlag remains an epistemological challenge in biology; unwise or implausible over‐interpretation of a given structure as such has led some to almost total skepticism as to its existence. Originating in botany in the 18th century it became applied to zoology (and humans) with increasing frequency over the last two centuries such that the very concept became widely discredited. Presently, atavisms have acquired a new life and reconsideration given certain reasonable criteria, including: Homology of structure of the postulated atavism to that of ancestral fossils or collateral species with plausible soft tissue reconstructions taking into account relationships of parts, obvious sites of origin and insertion of muscles, vascular channels, etc. Most parsimonious, plausible phylogenetic assumptions. Evident rudimentary or vestigial anatomical state in prior generations or in morphogenesis of a given organism. Developmental instability in prior generations, that is, some closely related species facultatively with or without the trait. Genetic identity or phylogenomic similarity inferred in ancestors and corroborated in more or less closely related species. Fluctuating asymmetry may be the basis for the striking evolutionary diversification and common atavisms in limbs; however, strong selection and developmental constraints would make atavisms in, for example, cardiac or CNS development less likely.Thus, purported atavisms must be examined critically in light of the above criteria. © 2013 Wiley Periodicals, Inc.

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D arwinian Evolution of Tumours

Chen

2017

Encyclopedia of Life Sciences

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Tumours as a human disease have been studied mostly from a mechanistic perspective in the past decades. It is now increasingly clear that tumourigenesis as an evolving process can be fully understood only in the light of evolution. Recent studies highlight the necessity of connecting the microevolution of a tumour with the macroevolution from unicellular life to metazoan multicellularity, which occurred ∼600 million years ago. With this background in mind, we discuss here the diverse, sometimes conflicting, views with regard to the driving forces of tumour evolution. Specifically, we show how mutation, selection, drift, migration, gain of function versus loss of function, genetic factors versus non‐genetic factors and deterministic forces versus stochasticity may affect the trajectory of a tumour evolution as well as our understanding. Key Concepts Tumourigenesis is a by‐product of the macroevolutionary event from unicellular life to metazoan multicellularity that occurred ∼600 million years ago. Tumour progression is a microevolutionary process of the asexual tumour cell population, driven in part by forces typical to organismal evolution. Unlike long‐term organismal evolution, which is driven exclusively by genetic forces, the short‐term tumour evolution can be affected heavily by epigenetic alterations. As a result, the decoupling between genetic divergence and expression divergence is expected. Tumour evolution represents a reversal of the macroevolution from unicellularity to multicellularity, by erasing the constraints evolved for the maintenance of multicellularity. As a result, loss of function plays a more important role than gain of function. Regardless of the external tissue environments, nearly all tumours evolve towards a predetermined cellular destination with properties typical to unicellular life. Tumour evolution is driven by both deterministic factors and stochastic factors. Recognition of this helps reconcile development and evolution, two distinct languages in the cancer research community, with the former spoken mostly by cell biologists who advocate fixed cellular programmes as driving forces and the latter spoken by geneticists who appreciate the apparent stochasticity of driver gene mutations.

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Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors

Cited by 215 publications

References 38 publications

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

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

Annals of morphology. Atavisms: Phylogenetic lazarus?

D arwinian Evolution of Tumours

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