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Updated: Jan 11, 2026
06:35
A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
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Senescent Fibroblasts Drive Melanoma Progression Through GCP-2 Induced CREB Phosphorylation Enhancing Glycolysis
Abhijit Basu1,2, Vida Farsam1, Karmveer Singh1,2
1Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
Aging Cell
|November 19, 2025
Summary
Senescent fibroblasts release chemokine GCP-2, promoting melanoma progression via CREB. Inhibiting CREB phosphorylation reduces tumor growth by altering melanoma cell metabolism, offering new therapeutic targets for older adults.
Area of Science:
- Oncology
- Cell Biology
- Aging Research
Background:
- Aging is the primary risk factor for melanoma progression.
- Factors secreted by senescent fibroblasts may drive melanoma, but mechanisms are unclear.
Purpose of the Study:
- To investigate the role of senescent fibroblast secretions in melanoma progression.
- To identify the molecular mechanisms linking aging, fibroblasts, and melanoma.
Main Methods:
- Assessed chemokine GCP-2 release from senescent fibroblasts in vitro and in aged melanoma patients.
- Investigated GCP-2 effects on melanoma cell lines and murine melanoma models.
- Analyzed CREB phosphorylation and metabolic shifts in response to GCP-2 inhibition.
Main Results:
- Senescent fibroblasts excessively release GCP-2.
- GCP-2 promotes melanoma oncogenic properties by enhancing glycolysis via CREB phosphorylation.
- Inhibiting CREB phosphorylation switches melanoma metabolism to oxidative phosphorylation, reducing tumor size.
Conclusions:
- Identified a novel axis: senescent fibroblast-GCP-2-CREB-metabolism driving melanoma progression.
- Targeting this axis offers potential therapeutic strategies for melanoma in older adults.
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