Regulation of Stem Cell Plasticity: Mechanisms and Relevance to Tissue Biology and Cancer
Open accessAbstract
Embryonic stem cells (ESCs) are associated with a high degree of plasticity, which allows them to self-renew and differentiate into every somatic cell. During differentiation, ESCs follow a hierarchically organized pattern towards tissue specificity, which ultimately results in permanent cell cycle arrest and a loss of cellular plasticity. In contrast to their normal somatic counterparts, cancer cells retain elevated levels of plasticity that include switches between epithelial and mesenchymal phenotypes. Transitions between these cell stages have lately been linked to the reacquisition of stem cell features during cellular reprogramming and dedifferentiation in normal and neoplastic cells. In this review, we discuss the key factors and their interplay that is needed to regain a stem cell stage with a particular emphasis put on the impact of cell cycle regulation. Apart from mechanistic insights into the emerging fundamental processes of stem cell plasticity and capacity to transdifferentiate, we also highlight implications of these concepts for tissue biology, tumorigenesis, and cancer therapy.
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Epithelial cell dedifferentiation is a critical cell state transition during tumorigenesis and confers tumor cells high proliferation capacity and progenitor-like fate through multidimensional reprogramming.
“Epithelial cell dedifferentiation is recognized as a critical cell state transition during tumorigenesis and confer tumor cells on high proliferation capacity and progenitor-like fate through multidimensional reprogramming1–3.”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [3]
Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · see citing works
Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells
Li, Z., Bao, S., Wu, Q., Wang, H., Eyler, C., Sathornsumetee, S., Shi, Q., Cao, Y., Lathia, J., McLendon, R. E., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.018 · Cited by 1,354 · see citing works
Suppression of induced pluripotent stem cell generation by the p53–p21 pathway
Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., & Yamanaka, S. (2009) · Nature · doi:10.1038/nature08235 · Cited by 1,301 · see citing works
Linking the p53 tumour suppressor pathway to somatic cell reprogramming
Kawamura, T., Suzuki, J., Wang, Y. V., Menendez, S., Morera, L. B., Raya, A., Wahl, G. M., & Belmonte, J. C. I. (2009) · Nature · doi:10.1038/nature08311 · Cited by 1,115 · see citing works
A specialized vascular niche for adult neural stem cells
Tavazoie, M., Van der Veken, L., Silva-Vargas, V., Louissaint, M., Colonna, L., Zaidi, B., Garcia-Verdugo, J. M., & Doetsch, F. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.025 · Cited by 1,033 · see citing works
A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity
Marión, R. M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M., & Blasco, M. A. (2009) · Nature · doi:10.1038/nature08287 · Cited by 1,028 · see citing works
Shen, Q., Wang, Y., Kokovay, E., Lin, G., Chuang, S.-M., Goderie, S. K., Roysam, B., & Temple, S. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.026 · Cited by 1,027 · see citing works
Cellular mechanisms of tumour suppression by the retinoblastoma gene
Burkhart, D. L., & Sage, J. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2399 · Cited by 974 · see citing works
Bracken, A. P., Kleine-Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., Theilgaard-Mönch, K., Minucci, S., Porse, B. T., Marine, J.-C., et al. (2007) · Genes & Development · doi:10.1101/gad.415507 · Cited by 850 · see citing works
p57 is required for quiescence and maintenance of adult hematopoietic stem cells
Matsumoto, A., Takeishi, S., Kanie, T., Susaki, E., Onoyama, I., Tateishi, Y., Nakayama, K., & Nakayama, K. I. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.06.014 · Cited by 329 · see citing works
Lack of p21 expression links cell cycle control and appendage regeneration in mice
Bedelbaeva, K., Snyder, A., Gourevitch, D., Clark, L., Zhang, X.-M., Leferovich, J., Cheverud, J. M., Lieberman, P., & Heber-Katz, E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000830107 · Cited by 207 · see citing works
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Zhang, Z., Wu, Y., Fu, J., Yu, X., Su, Y., Jia, S., Cheng, H., Shen, Y., He, X., Ren, K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48173-9 · Cited by 14 · see citing works
- Authors
- Strauss, R., Hamerlik, P., Lieber, A., & Bartek, J.
- Affiliations
- Danish Cancer Society (DK)
- Institute of Molecular and Translational Medicine (CZ)
- University of Washington (US)
- Corresponding author
- Strauss, Robert
- Bartek, Jiri
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 20
- Issue
- 5
- Pages
- 887-897
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC3345979
- OpenAlex
- W1986357487
- Cited by
- 41
- References
- 11
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 2 · 2023: 2 · 2021: 3 · 2020: 2 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 2
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA136487)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- stem cell plasticity, embryonic stem cells, transdifferentiation, epithelial-mesenchymal transition, cell cycle regulation, cellular reprogramming, dedifferentiation, cancer stemness, carcinogenesis, cancer therapy, tissue biology
- MeSH terms
- Animals, Cell Cycle, Cell Differentiation, Cell Transformation, Neoplastic, Humans, Neoplasms, Biomarkers, Tumor, Neoplastic Stem Cells, Gene Expression Regulation, Neoplastic, Cell Cycle Proteins, Mice, Embryonic Stem Cells, Cell Dedifferentiation, Epithelial-Mesenchymal Transition
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