ArticlePloS one2014
CoCl2, a mimic of hypoxia, induces formation of polyploid giant cells with stem characteristics in colon cancer.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 142 citations in OpenAlex.
- Atypical fusion among non-malignant cells: Unveiling the link between post-fusion-induced genome chaos and cancer initiation.Cancer cell international · 2026Article
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- RHAMM drives formation of polyploid cancer cells and confers resistance to ER-targeted therapy in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sodium Sulfite as an Oxygen-Depletion-Based Chemical Model of Tumor Hypoxia In Vitro.Applied biochemistry and biotechnology · 2026Article
- Hyperwrinkling of the nuclear lamina is associated with attenuated mechanosensitivity in giant nucleated cancer cells.Science advances · 2026Article
- Clinical Implications of Polyploid Giant Cancer Cells in Solid Tumors: Biology, Diagnosis, and Therapeutic Considerations.Cancers · 2026Review
- Pervasive chromosomal instability drives the karyotypic evolution of hypodiploid tumours.Genome medicine · 2026Article
- Polyploid Giant Cancer Cells as a Senescence-Linked State in the Tumor Microenvironment.Cancers · 2026Review
- Etiology of polyploid giant cancer cells: a new frontier in cancer biology.Cancer cell international · 2026Review
- Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation.Scientific reports · 2026Article
- Cross-talk between cancer-associated fibroblasts and dormant cancer cells: current status and promising therapeutic potential.Cancer cell international · 2025Review
- The Impact of Polyploid Giant Cancer Cells: The Root of Stress Resilience.Cancer science · 2025Review
- Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation.bioRxiv : the preprint server for biology · 2025Article
- Article
- Emerging Paradigms in Cancer Metastasis: Ghost Mitochondria, Vasculogenic Mimicry, and Polyploid Giant Cancer Cells.Cancers · 2024Review
- Polyploid cancer cells reveal signatures of chemotherapy resistance.bioRxiv : the preprint server for biology · 2024Article
- Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation.Cancer research communications · 2024Article
- Dormant cancer cells and polyploid giant cancer cells: The roots of cancer recurrence and metastasis.Clinical and translational medicine · 2024Review
- Polyploid giant cancer cells: origin, possible pathways of formation, characteristics, and mechanisms of regulation.Frontiers in cell and developmental biology · 2024Review
- Domperidone Exerts Antitumor Activity in Triple-Negative Breast Cancer Cells by Modulating Reactive Oxygen Species and JAK/STAT3 Signaling.Biomolecules & therapeutics · 2023Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The induction of polyploidy is considered the reproductive end of cells, but there is evidence that polyploid giant cancer cells (PGCCs) contribute to cell repopulation during tumor relapse. However, the role of these cells in the development, progression and response to therapy in colon cancer remains undefined. Therefore, the main objective of this study was to investigate the generation of PGCCs in colon cancer cells and identify mechanisms of formation. Treatment of HCT-116 and Caco-2 colon cancer cells with the hypoxia mimic CoCl2 induced the formation of cells with larger cell and nuclear size (PGCCs), while the cells with normal morphology were selectively eliminated. Cytometric analysis showed that CoCl2 treatment induced G2 cell cycle arrest and the generation of a polyploid cell subpopulation with increased cellular DNA content. Polyploidy of hypoxia-induced PGCCs was confirmed by FISH analysis. Furthermore, CoCl2 treatment effectively induced the stabilization of HIF-1α, the differential expression of a truncated form of p53 (p47) and decreased levels of cyclin D1, indicating molecular mechanisms associated with cell cycle arrest at G2. Generation of PGCCs also contributed to expansion of a cell subpopulation with cancer stem cells (CSCs) characteristics, as indicated by colonosphere formation assays, and enhanced chemoresistance to 5-fluorouracil and oxaliplatin. In conclusion, the pharmacological induction of hypoxia in colon cancer cells causes the formation of PGCCs, the expansion of a cell subpopulation with CSC characteristics and chemoresistance. The molecular mechanisms involved, including the stabilization of HIF-1 α, the involvement of p53/p47 isoform and cell cycle arrest at G2, suggest novel targets to prevent tumor relapse and treatment failure in colon cancer.
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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.