Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts
Open accessAbstract
Depending on the cell type and tissue environment, epithelial and mesenchymal cell phenotypes are not static and can be highly dynamic. Epithelial-mesenchymal transitions (EMTs) and reverse EMTs provide flexibility during embryogenesis. While EMTs are a critical normal process during development and wound healing, properties of the EMT have been implicated in human pathology, particularly cancer metastasis. A normal undamaged epithelium does not typically exhibit features of an EMT. However, particularly under the influence of the surrounding microenvironment, cancer cells may reactivate developmental phenotypes out of context in the adult. This reactivation, such as the EMT, can facilitate tumor cell invasion and metastasis, and therefore is a major mechanism of tumor progression. Conversely, cellular senescence, which is associated with aging, is a process by which cells enter a state of permanent cell cycle arrest, thereby constituting a potent tumor suppressive mechanism. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into pro-inflammatory cells having the ability to promote tumor progression, in part by inducing an EMT in nearby epithelial cells. Here, we summarize the potential impacts of SASP factors, particularly interleukins, on tissue microenvironments and their ability to stimulate tumor progression through induction of an EMT.
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Senescent fibroblasts induce EMT in premalignant epithelial cells and nonaggressive cancer epithelial cells in part through secretion of IL-6 and IL-8.
“Senescent fibroblasts induce an epithelial-to-mesenchymal transition in premalignant epithelial cells and nonaggressive cancer epithelial cells in part through the secretion of IL-6 and IL-8 (32, 102, 118).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [102]
The sections “Effects of the SASP on Cell Migration and Invasion” and “Effects of the SASP on Epithelial Cell Proliferation and Differentiation” report EMT in nonaggressive breast cancer cells and attribute EMT-like changes in mammary epithelial cells partly to IL-6 and IL-8. For premalignant epithelial cells, the paper describes stimulated growth or progression, not an IL-6/IL-8-mediated EMT. Page numbers are not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSASP factors can stimulate malignant phenotypes in culture.
“In addition to stimulating tumor growth in mice, SASP factors can stimulate malignant phenotypes in culture.”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [102]
One such malignant phenotype is the epithelial-to-mesenchymal transition.
“One such phenotype is the epithelial-to-mesenchymal transition (102) (Figure 2).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [102]
The SASP can have a major impact on various biological processes, including cell proliferation, angiogenesis, inflammation, epithelial-to-mesenchymal transition, tissue repair and wound healing.
“The SASP can have a major impact on various biological processes, including cell proliferation, angiogenesis, inflammation16, epithelial-to-mesenchymal transition17, tissue repair18 and wound healing3 (Fig. 2).”
From Spatial mapping of cellular senescence: emerging challenges and opportunities (2023) · cites this paper as [17]
A known pathway for SASP-promoted cancer metastasis is the induction of epithelial to mesenchymal transition.
“A known pathway for SASP-promoted cancer metastasis is the induction of epithelial to mesenchymal transition (EMT)”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [106]
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- Authors
- Laberge, R.-M., Awad, P., Campisi, J., & Desprez, P.-Y.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Desprez, Pierre-Yves
- Venue
- Cancer Microenvironment
- Published
- 2011-06-25
- Volume
- 5
- Issue
- 1
- Pages
- 39-44
- ISSN
- 1875-2284 (ISSN-L)
- 1875-2292
- PMC
- PMC3343197
- OpenAlex
- W2083594352
- Cited by
- 255
- References
- 65
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 26 · 2023: 20 · 2022: 17 · 2021: 20 · 2020: 22 · 2019: 15 · 2018: 20 · 2017: 24 · 2016: 13 · 2015: 12 · 2014: 15 · 2013: 14 · 2012: 9
- FWCI
- 8.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Microenvironment (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- epithelial-mesenchymal transition, cellular senescence, senescence-associated secretory phenotype, senescent fibroblasts, tumor progression, metastasis, tumor microenvironment, interleukins, tumor invasion
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