Senescence-associated secretory phenotype favors the emergence of cancer stem-like cells
Open accessAbstract
The molecular mechanisms underlying cancer resistance remain elusive. One possible explanation is that cancer stem cells (CSCs) elude drug treatment, emerge and reproduce a tumor. Using multiple myeloma as a paradigm, we showed that cancer stem-like cells (CSLCs) appear after genotoxic stress because of their intrinsic properties. However, these properties do not drive the emergence of the CSLCs. Following genotoxic stress, remaining DNA damages lead to a senescence-associated secretory phenotype (SASP). Senescent cells, which are the non-CSLCs, secrete chemokines contributing to the emergence, maintenance and migration of CSLCs. Downregulation of checkpoint protein 2, a key player of SASP, significantly reduced the emergence of CSLCs. Our results unravel a novel molecular mechanism by which SASP might promote malignancy, underlining the dual role of senescence in tumorigenesis. This mechanism, based on mutual cooperation among tumor cells, illustrates how cancer may relapse; its targeting could represent new therapeutic opportunities.
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Co-culturing undifferentiated myeloma cells in conditioned media from senescent myeloma cells promotes the emergence, maintenance, and migration of cancer stem-like cells.
“Similarly, co-culturing undifferentiated myeloma cells in conditioned media from senescent myeloma cells promotes the emergence, maintenance, and migration of cancer stem-like cells.64”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [64]
The SASP is able to inhibit differentiation both in vitro and in vivo, while in some cases leads to acquisition of stem cell characteristics.
“Interestingly, the SASP is able to inhibit differentiation both in vitro and in vivo, while in some cases leads to acquisition of stem cell characteristics.41,44,54,55,64–66”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [64]
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- Authors
- Cahu, J., Bustany, S., & Sola, B.
- Affiliations
- Centre Hospitalier Universitaire de Caen Normandie (FR)
- Corresponding author
- Cahu, J
- ORCID
- Sola, B
- Venue
- Cell Death & Disease
- Published
- 2012-12-20
- Volume
- 3
- Issue
- 12
- Pages
- e446-e446
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3542619
- OpenAlex
- W2080339543
- Cited by
- 160
- References
- 34
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 15 · 2023: 11 · 2022: 11 · 2021: 25 · 2020: 12 · 2019: 12 · 2018: 13 · 2017: 9 · 2016: 17 · 2015: 8 · 2014: 7 · 2013: 10
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Ligue Contre le Cancer
- Région Normandie
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Keywords
- senescence-associated secretory phenotype, cancer stem-like cells, multiple myeloma, genotoxic stress, DNA damage, chemokines, tumor recurrence, tumor resistance, senescence, carcinogenesis
- MeSH terms
- Animals, Cell Movement, Cell Survival, DNA Damage, Female, Humans, Mice, Nude, Multiple Myeloma, Phenotype, Neoplastic Stem Cells, Cellular Senescence, Protein Serine-Threonine Kinases, Chemokines, Protein Transport, Cell Line, Tumor, Mice, Checkpoint Kinase 2
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