Inactivation 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.

Automated summary

Studies have shown that melanoma-derived extracellular vesicles (EVs) play a role in lymph node metastasis, with EMILIN-1 being proteolyzed and secreted in small EVs as a mechanism to reduce its intracellular levels and promote metastasis in mouse melanoma lymph node metastatic cells. EMILIN-1 exhibits tumor and metastasis suppressive properties, reducing effective migration, cell viability, primary tumor growth, and metastasis.