ArticleCell death and differentiation2015
Age-associated inflammation connects RAS-induced senescence to stem cell dysfunction and epidermal malignancy.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
42 citing papers in PubMed.
- Integrative analysis of single-cell and bulk transcriptome data reveals age-related immune cell alterations in primary glioblastoma associated with prognosis.Cancer immunology, immunotherapy : CII · 2025Article
- Age-Related Changes in Myeloid Cells and Their Impact on Subcutaneous Melanoma Growth in Mice.Aging and cancer · 2025Article
- Irradiation‑induced cellular senescence is linked to pro‑survival signaling and checkpoint regulation in a 2D and 3D model for head and neck cancer.Oncology reports · 2025Article
- Comprehensive bioinformatics analysis of MEX3 family genes in hepatocellular carcinoma.Scientific reports · 2025Article
- Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways.Molecular cancer · 2025Review
- The complex interplay between aging and cancer.Nature aging · 2025Review
- The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.Theranostics · 2025Review
- Role of local angiotensin II signaling in bladder function.American journal of physiology. Renal physiology · 2024Review
- Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.Cancer communications (London, England) · 2024Review
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- Considerations and Approaches for Cancer Immunotherapy in the Aging Host.Cancer immunology research · 2023Review
- p16Lupus science & medicine · 2023Article
- Locally sourced: site-specific immune barriers to metastasis.Nature reviews. Immunology · 2023Review
- Impact of Senolytic Treatment on Gene Expression in Aged Lung.International journal of molecular sciences · 2023Article
- Review
- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
- ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Leucine Supplementation in Middle-Aged Male Mice Improved Aging-Induced Vascular Remodeling and Dysfunction via Activating the Sirt1-Foxo1 Axis.Nutrients · 2022Article
- Single-cell transcriptomics reveals a senescence-associated IL-6/CCR6 axis driving radiodermatitis.EMBO molecular medicine · 2022Article
- Does Inflammation Contribute to Cancer Incidence and Mortality during Aging? A Conceptual Review.Cancers · 2022Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is the single biggest risk factor for malignant transformation. Among the most common age-associated malignancies are non-melanoma skin cancers, comprising the most common types of human cancer. Here we show that mutant H-Ras activation in mouse epidermis, a frequent event in cutaneous squamous cell carcinoma (SCC), elicits a differential outcome in aged versus young mice. Whereas H-Ras activation in the young skin results in hyperplasia that is mainly accompanied by rapid hair growth, H-Ras activation in the aged skin results in more dysplasia and gradual progression to in situ SCC. Progression is associated with increased inflammation, pronounced accumulation of immune cells including T cells, macrophages and mast cells as well as excessive cell senescence. We found not only an age-dependent increase in expression of several pro-inflammatory mediators, but also activation of a strong anti-inflammatory response involving enhanced IL4/IL10 expression and immune skewing toward a Th2 response. In addition, we observed an age-dependent increase in the expression of Pdl1, encoding an immune suppressive ligand that promotes cancer immune evasion. Moreover, upon switching off oncogenic H-Ras activity, young but not aged skin regenerates successfully, suggesting a failure of the aged epidermal stem cells to repair damaged tissue. Our findings support an age-dependent link between accumulation of senescent cells, immune infiltration and cancer progression, which may contribute to the increased cancer risk associated with old age.
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