ArticlePLoS computational biology2014
Effect of dedifferentiation on time to mutation acquisition in stem cell-driven cancers.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 66 citations in OpenAlex.
- A damage-structured PDE model of stem cell hierarchies: The dual role of dedifferentiation in tissue homeostasis and aging.PloS one · 2026Article
- Cell competition within breast tumor microenvironment: emerging role of cancer stem cells and immune cells in tumor progression and therapeutic implications.Frontiers in oncology · 2026Review
- Transcriptomics of mussel transmissible cancer MtrBTN2 suggests accumulation of multiple cancer traits and oncogenic pathways shared among bilaterians.Open biology · 2023Article
- Upregulation of KIF11 in TP53 Mutant Glioma Promotes Tumor Stemness and Drug Resistance.Cellular and molecular neurobiology · 2022Article
- Functional genomics of AP-2α and AP-2γ in cancers: in silico study.BMC medical genomics · 2020Article
- The effects of phenotypic plasticity on the fixation probability of mutant cancer stem cells.Journal of theoretical biology · 2020Article
- RpS13 controls the homeostasis of germline stem cell niche through Rho1-mediated signals in the Drosophila testis.Cell proliferation · 2020Article
- The evolution of metapopulation dynamics and the number of stem cells in intestinal crypts and other tissue structures in multicellular bodies.Evolutionary applications · 2020Review
- Effects of ordered mutations on dynamics in signaling networks.BMC medical genomics · 2020Article
- Nutlin-3-Induced Sensitization of Non-Small Cell Lung Cancer Stem Cells to Axitinib-Induced Apoptosis Through Repression of Akt1/Wnt Signaling.Oncology research · 2019Article
- Modeling breast cancer progression to bone: how driver mutation order and metabolism matter.BMC medical genomics · 2019Article
- Role of mTORC1 in intestinal epithelial repair and tumorigenesis.Cellular and molecular life sciences : CMLS · 2019Review
- The invasion of de-differentiating cancer cells into hierarchical tissues.PLoS computational biology · 2019Article
- The biological characteristics of transcription factors AP-2α and AP-2γ and their importance in various types of cancers.Bioscience reports · 2019Review
- The Air Sac Primordium ofInternational journal of molecular sciences · 2018Review
- Effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells in mathematical models with feedback regulation.Journal of theoretical biology · 2018Article
- An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia.Journal of hematology & oncology · 2017Article
- Cell dynamics in tumour environment after treatments.Journal of the Royal Society, Interface · 2017Article
- Phenotypic heterogeneity in modeling cancer evolution.PloS one · 2017Article
- Emergence of heterogeneity in acute leukemias.Biology direct · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence suggests that many tumors have a hierarchical organization, with the bulk of the tumor composed of relatively differentiated short-lived progenitor cells that are maintained by a small population of undifferentiated long-lived cancer stem cells. It is unclear, however, whether cancer stem cells originate from normal stem cells or from dedifferentiated progenitor cells. To address this, we mathematically modeled the effect of dedifferentiation on carcinogenesis. We considered a hybrid stochastic-deterministic model of mutation accumulation in both stem cells and progenitors, including dedifferentiation of progenitor cells to a stem cell-like state. We performed exact computer simulations of the emergence of tumor subpopulations with two mutations, and we derived semi-analytical estimates for the waiting time distribution to fixation. Our results suggest that dedifferentiation may play an important role in carcinogenesis, depending on how stem cell homeostasis is maintained. If the stem cell population size is held strictly constant (due to all divisions being asymmetric), we found that dedifferentiation acts like a positive selective force in the stem cell population and thus speeds carcinogenesis. If the stem cell population size is allowed to vary stochastically with density-dependent reproduction rates (allowing both symmetric and asymmetric divisions), we found that dedifferentiation beyond a critical threshold leads to exponential growth of the stem cell population. Thus, dedifferentiation may play a crucial role, the common modeling assumption of constant stem cell population size may not be adequate, and further progress in understanding carcinogenesis demands a more detailed mechanistic understanding of stem cell homeostasis.
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