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

oleh: Ana Amor López, Marina S. Mazariegos, Alessandra Capuano, Pilar Ximénez-Embún, Marta Hergueta-Redondo, Juan Ángel Recio, Eva Muñoz, Fátima Al-Shahrour, Javier Muñoz, Diego Megías, Roberto Doliana, Paola Spessotto, Héctor Peinado

Format: Article
Diterbitkan: MDPI AG 2021-07-01

Deskripsi

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.