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

Source: https://onco.cc/key-papers/paper-trigos-proc-natl-acad-sci-u-s-a/  
OnCo record `paper-trigos-proc-natl-acad-sci-u-s-a` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one term page, indexed on Europe PMC as PubMed record 28484005 and published in Proceedings of the National Academy of Sciences; the citing page links this DOI, which is how the record was matched.

## Summary

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.

Indexed on Europe PMC as PubMed record 28484005 (DOI 10.1073/pnas.1617743114). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Proceedings of the National Academy of Sciences
- Year: 2017
- DOI: 10.1073/pnas.1617743114
- Authors: Trigos AS, Pearson RB, Papenfuss AT, et al.
- What it means: One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Proc Natl Acad Sci U S A 2017: https://doi.org/10.1073/pnas.1617743114
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28484005/
- Europe PMC: https://europepmc.org/article/MED/28484005

## Connected records

- terms: [Atavistic theory: cancer as a reversion to an ancient programme](https://onco.cc/terms/atavistic-theory-of-cancer/)
- journals: [Proceedings of the National Academy of Sciences](https://onco.cc/journals/pnas/)

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