The Senescence–Stemness Alliance – A Cancer-Hijacked Regeneration Principle
Abstract
Activated oncogenes or anticancer therapies evoke senescent cell-cycle arrest in (pre-)malignant cells, thereby interrupting tumor formation or progression. Physiologically, cellular senescence contributes to embryonic development and tissue regeneration. These observations and the overlap of numerous gene products in senescence and stem cell signaling prompted investigations into whether epigenetic establishment of the senescent state may concomitantly reprogram the cell into a latent stem-like condition, whose functional impact becomes evident when arrested cells resume proliferation. We review here recent discoveries underscoring the unexpected senescence-stemness alliance, elucidate underlying molecular mechanisms, and discuss its fundamentally different implications in normal tissue repair - to replenish the exhausted repopulation capacity - as compared to cancer biology, where usurpation of this natural principle accounts for particularly aggressive tumor behavior.
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Therapy-induced senescence (TIS) promotes stem cell and self-renewing features, which can contribute to cancer initiation and aggressiveness.
“Therapy-induced senescence (TIS) also promotes stem cell and self-renewing features, which can contribute to cancer initiation and aggressiveness (Milanovic et al. 2018).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Milanovic et al. 2018
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Senescence and the SASP: many therapeutic avenues
Birch, J., & Gil, J. (2020) · Genes & Development · doi:10.1101/gad.343129.120 · Cited by 1,177 · see citing works
“For instance, the mTOR inhibitor rapamycin increases life span and health span (Miller et al. 2011) and acts as a selective SASP suppressor.”
BackgroundSenescence in Post-Mitotic Cells: A Driver of Aging?
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- Authors
- Milanovic, M., Yu, Y., & Schmitt, C. A.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Max Delbrück Center (DE)
- Corresponding author
- Schmitt, Clemens A.
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 28
- Issue
- 12
- Pages
- 1049-1061
- ISSN
- 0962-8924 (ISSN-L)
- OpenAlex
- W2893557363
- Cited by
- 92
- References
- 32
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 10 · 2023: 20 · 2022: 8 · 2021: 20 · 2020: 13 · 2019: 10 · 2018: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Helmholtz Association (HA-305)
- Deutsche Krebshilfe (110678)
- Berlin School of Integrative Oncology
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cellular senescence, stemness, tissue regeneration, tissue repair, cell cycle arrest, oncogenes, epigenetic reprogramming, tumor repopulation, stem cell signaling
- MeSH terms
- Animals, Humans, Neoplasms, Regeneration, Stem Cells, Cellular Senescence, Cell Cycle Checkpoints
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