ArticleProceedings of the National Academy of Sciences of the United States of America2017
Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 4 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- Inflamed Yet Immune-Evasive? A Transcriptomic Meta-Analysis Identifies Conserved Inflammatory, Developmental, and Neuronal Signatures Associated with Polyploid Giant Cancer Cells.International journal of molecular sciences · 2026Pooled it
- Systemic Alterations of Cancer Cells and Their Boost by Polyploidization: Unicellular Attractor (UCA) Model.International journal of molecular sciences · 2023Pooled it
- Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine.International journal of molecular sciences · 2022Pooled it
- Pooled it
- The "Selfish Cell": The Central Role of Metabolism in Relaying Environmental Stimuli and Controlling Cellular Function.Biology · 2026Review
- In Silico Identification of Conserved 'Fungal Islands' in Human Septin9: Evidence for Atavistic Therapeutic Targets.International journal of molecular sciences · 2026Article
- Tracing Genetic Images Formed During Evolution.International journal of molecular sciences · 2026Article
- Exonic enhancers are a widespread class of dual-function regulatory elements.Nature communications · 2026Article
- Bleb-based extravasation uses conserved morphodynamics but divergent calcium control.Nature communications · 2026Article
- Disrupting Lipid Raft Microdomains to Block Polyploid Giant Cancer Cell Budding and Enhance Radiotherapy Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of cancer mini-drivers by deciphering selective landscape in the cancer genome.Briefings in bioinformatics · 2026Article
- Reconstruction of the evolutionary landscape of biological processes involved in the early stages of the metastatic cascade.Genetics and molecular biology · 2026Article
- Understanding cancer as a systemic disease through comprehension of neural stemness as the core property of cancer cell and the basic rules it dictates.Frontiers in cell and developmental biology · 2026Review
- Cancer as an evolutionary reversal-time for a paradigm shift.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Article
- Identification of Chondroitin Polymerizing Factor as a Biomarker for Colorectal Cancer by the Human Villi Development Model.Cancer innovation · 2025Article
- Polyploid giant cancer cells (PGCC): short-term return to multicellularity.Biological research · 2025Article
- Coevolution of cooperative lifestyles and reduced cancer prevalence in mammals.Science advances · 2025Article
- Evolutionary Transcriptomics of Cancer Development.International journal of molecular sciences · 2025Article
- Article
- Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer.Nucleic acids research · 2025Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.