Ultraviolet light-induced collagen degradation inhibits melanoma invasion

Timothy Budden, Caroline Gaudy-Marqueste, Andrew Porter, Emily Kay, Shilpa Gurung, Charles H. Earnshaw, Katharina Roeck, Sarah Craig, Víctor Traves, Jean Krutmann, Patricia Muller, Luisa Motta, Sara Zanivan, Angeliki Malliri, Simon J. Furney, Eduardo Nagore, Amaya Virós

Research output: Contribution to journalArticlepeer-review


Ultraviolet radiation (UVR) damages the dermis and fibroblasts; and increases melanoma incidence. Fibroblasts and their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, the extracellular matrix (ECM) and melanoma invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving matrix metalloprotein-1 (MMP1) expression, reducing local collagen (COL1A1), and COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, inhibiting ECM degradation and MMP1 expression restored melanoma invasion. Primary cutaneous melanomas of aged humans show more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen, and collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. Thus, primary melanomas arising over collagen-degraded skin are less invasive, and reduced invasion improves survival. However, melanoma-associated fibroblasts can restore invasion by increasing collagen synthesis. Finally, high COL1A1 gene expression is a biomarker of poor outcome across a range of primary cancers.
Original languageEnglish
Article number2742
JournalNature Communications
Issue number1
Publication statusPublished - 12 May 2021


  • Collagen Type I, alpha 1 Chain
  • Collagen Type I/genetics
  • Collagen/metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts/metabolism
  • Humans
  • Lentivirus/genetics
  • Mass Spectrometry
  • Matrix Metalloproteinase 1/genetics
  • Melanoma/metabolism
  • Microscopy, Atomic Force
  • Ultraviolet Rays

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


Dive into the research topics of 'Ultraviolet light-induced collagen degradation inhibits melanoma invasion'. Together they form a unique fingerprint.

Cite this