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Polyploid giant cancer cells (PGCC): short-term return to multicellularity
Alexander E Vinogradov1,2, Olga V Anatskaya3,4
1Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia. aevin@incras.ru.
Biological Research
|November 25, 2025
Summary
Giant polyploid cancer cells (PGCC) exhibit a transient return to multicellularity, potentially explaining their treatment resistance. Common polyploid cells, however, show a backward evolutionary shift towards unicellular traits.
Area of Science:
- Cancer Biology
- Evolutionary Developmental Biology
- Genomics
Background:
- Polyploidization is a hallmark of cancer progression, increasing malignancy.
- Common polyploid cancer cells are prevalent in tumors and metastases.
- Giant polyploid cancer cells (PGCC) emerge under stress and exhibit treatment resistance.
Purpose of the Study:
- To investigate the transcriptomic differences between common polyploid cancer cells and giant polyploid cancer cells (PGCC).
- To explore the evolutionary implications of gene expression patterns in polyploid cancer cells.
- To understand the basis of treatment resistance in PGCC.
Main Methods:
- Transcriptome meta-analysis of various polyploid cancer cell types.
- Analysis of gene expression patterns, including unicellular (UC) and stemness genes.
- Protein interactome centrality analysis.
- Principal component analysis of transcriptome profiles along the gene evolutionary age axis.
Main Results:
- Common polyploid cells upregulate UC and stemness genes, indicating a 'serial atavism' towards unicellularity.
- PGCC suppress UC and stemness genes, upregulating multicellular genes, suggesting a transient return to multicellularity.
- This multicellular shift in PGCC is more pronounced in early progeny and diminishes over time, irrespective of cancer origin or inducing stress.
Conclusions:
- PGCC represent a unique phenomenon of transient multicellularity linked to collective treatment resistance.
- Gene expression patterns in polyploid cancer cells are strongly influenced by evolutionary age.
- The evolutionary basis of gene expression offers a framework for understanding cancer biology and regenerative medicine.
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