biostudies-literatureAmor Lopez AFundación Bancaria Caixa d'Estalvis i Pensions de BarcelonaFundación FeroMinisterio de Economía, Industria y Competitividad, Gobierno de EspañaFundación Bancaria Caixa d'Estalvis i Pensions de BarcelonaFundación Científica Asociación Española Contra el Cáncer7406https://www.ebi.ac.uk/biostudies/studies/S-EPMC8303474biostudies-literatureUnknown22(14)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.International journal of molecular sciencesInactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis.PMC8303474N/ASAF2014-54541-RRecio JAAl-Shahrour FSpessotto PMazariegos MSCapuano AXimenez-Embun PMunoz JHergueta-Redondo MDoliana RMegias DPeinado HAmor Lopez AMunoz EfalseInactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis.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.2021-01-01T00:00:00Z2021 Jul2026-05-01T03:06:47.106Z2022-02-11T00:11:07.979ZS-EPMC83034743429902510.3390/ijms22147406