Related Experiment Video
Updated: Apr 16, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
The reverse evolution from multicellularity to unicellularity during carcinogenesis
Han Chen1, Fangqin Lin1, Ke Xing2
1Key Laboratory of Gene Engineering of Ministry of Education, Cooperative Innovation Center for High Performance Computing, College of Ecology and Evolution, Sun Yat-sen University, Guangzhou 510275, China.
Abstract:
Theoretical reasoning suggests that cancer may result from a knockdown of the genetic constraints that evolved for the maintenance of metazoan multicellularity. By characterizing the whole-life history of a xenograft tumour, here we show that metastasis is driven by positive selection for general loss-of-function mutations on multicellularity-related genes. Expression analyses reveal mainly downregulation of multicellularity-related genes and an evolving expression profile towards that of embryonic stem cells, the cell type resembling unicellular life in its capacity of unlimited clonal proliferation. Also, the emergence of metazoan multicellularity ~600 Myr ago is accompanied by an elevated birth rate of cancer genes, and there are more loss-of-function tumour suppressors than activated oncogenes in a typical tumour. These data collectively suggest that cancer represents a loss-of-function-driven reverse evolution back to the unicellular 'ground state'. This cancer evolution model may account for inter-/intratumoural genetic heterogeneity, could explain distant-organ metastases and hold implications for cancer therapy.
Insights
Cancer may be reverse evolution. Metastasis is driven by loss-of-function mutations in genes crucial for multicellularity, reverting cells to a unicellular state.
Area of Science:
- Evolutionary biology
- Cancer biology
- Genetics
Background:
- Metazoan multicellularity evolved complex genetic constraints.
- Cancer's origins and progression remain incompletely understood.
- Theoretical models link cancer to disruptions in these multicellularity constraints.
Purpose of the Study:
- To investigate the role of multicellularity genes in cancer metastasis.
- To characterize the evolutionary trajectory of a xenograft tumor.
- To explore the relationship between cancer gene evolution and multicellularity.
Main Methods:
- Whole-life history characterization of a xenograft tumor.
- Analysis of gene expression patterns.
- Comparative analysis of cancer gene birth rates and mutation types.
Main Results:
- Metastasis is driven by positive selection for loss-of-function mutations in multicellularity genes.
- Downregulation of multicellularity genes and an expression profile shift towards embryonic stem cells were observed.
- Cancer gene evolution shows an elevated birth rate, with a prevalence of loss-of-function tumor suppressors.
Conclusions:
- Cancer represents a reverse evolution towards a unicellular state, driven by loss-of-function mutations.
- This model explains tumor heterogeneity, distant metastases, and has therapeutic implications.
- Understanding cancer as dedifferentiation provides a new framework for treatment strategies.
Related Concept Videos
02:21Cancers Originate from Somatic Mutations in a Single Cell
02:21Cancers Originate from Somatic Mutations in a Single Cell
02:38Mitogens and the Cell Cycle
01:24Eukaryotic Evolution
Contrary to the endosymbiont theory, the eukaryote-first hypothesis proposes that the simpler prokaryotic and...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...