Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis

Int J Mol Sci. 2021 Jul 9;22(14):7406. doi: 10.3390/ijms22147406.


Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.

Keywords: EMILIN-1; melanoma; metastasis; small extracellular vesicles.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Computational Biology
  • Extracellular Vesicles / metabolism*
  • Lymphatic Metastasis / genetics
  • Male
  • Mass Spectrometry
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Proteolysis
  • RNA-Seq
  • Real-Time Polymerase Chain Reaction
  • Statistics, Nonparametric
  • Up-Regulation
  • Xenograft Model Antitumor Assays


  • Membrane Glycoproteins
  • elastin microfibril interface located protein