Inactivation of emilin-1 by proteolysis and secretion in small extracellular vesicles favors melanoma progression and metastasis: International Journal of Molecular Sciences

A. Amor López, M.S. Mazariegos, A. Capuano, P. Ximénez-Embún, M. Hergueta-Redondo, J.Á. Recio, E. Muñoz, F. Al-Shahrour, J. Muñoz, D. Megías, R. Doliana, P. Spessotto, H. Peinado

Research output: Contribution to journalArticlepeer-review

Abstract

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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
Article number7406
Number of pages17
JournalInt. J. Mol. Sci.
Volume22
Issue number14
DOIs
Publication statusPublished - 2021

Keywords

  • EMILIN-1
  • Melanoma
  • Metastasis
  • Small extracellular vesicles
  • elastin microfibril interface located protein
  • membrane protein
  • animal
  • biology
  • C57BL mouse
  • cell motion
  • cell proliferation
  • cell survival
  • drug screening
  • exosome
  • genetics
  • lymph node metastasis
  • male
  • mass spectrometry
  • melanoma
  • metabolism
  • mouse
  • nonparametric test
  • pathology
  • protein degradation
  • real time polymerase chain reaction
  • tumor cell line
  • upregulation
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Computational Biology
  • Extracellular Vesicles
  • Lymphatic Metastasis
  • Male
  • Mass Spectrometry
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Proteolysis
  • Real-Time Polymerase Chain Reaction
  • RNA-Seq
  • Statistics, Nonparametric
  • Up-Regulation
  • Xenograft Model Antitumor Assays

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