Inhibition of cholesterol transport impairs Cav-1 trafficking and small extracellular vesicles secretion, promoting amphisome formation in melanoma cells

© 2023 The Authors. Traffic published by John Wiley & Sons Ltd..

Caveolin-1 (Cav-1) is a fundamental constituent of caveolae, whose functionality and structure are strictly dependent on cholesterol. In this work the U18666A inhibitor was used to study the role of cholesterol transport in the endosomal degradative-secretory system in a metastatic human melanoma cell line (WM266-4). We found that U18666A induces a shift of Cav-1 from the plasma membrane to the endolysosomal compartment, which is involved, through Multi Vesicular Bodies (MVBs), in the formation and release of small extracellular vesicles (sEVs). Moreover, this inhibitor induces an increase in the production of sEVs with chemical-physical characteristics similar to control sEVs but with a different protein composition (lower expression of Cav-1 and increase of LC3II) and reduced transfer capacity on target cells. Furthermore, we determined that U18666A affects mitochondrial function and also cancer cell aggressive features, such as migration and invasion. Taken together, these results indicate that the blockage of cholesterol transport, determining the internalization of Cav-1, may modify sEVs secretory pathways through an increased fusion between autophagosomes and MVBs to form amphisome, which in turn fuses with the plasma membrane releasing a heterogeneous population of sEVs to maintain homeostasis and ensure correct cellular functionality.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

Traffic (Copenhagen, Denmark) - 24(2023), 2 vom: 10. Feb., Seite 76-94

Sprache:

Englisch

Beteiligte Personen:

Peruzzu, Daniela [VerfasserIn]
Boussadia, Zaira [VerfasserIn]
Fratini, Federica [VerfasserIn]
Spadaro, Francesca [VerfasserIn]
Bertuccini, Lucia [VerfasserIn]
Sanchez, Massimo [VerfasserIn]
Carollo, Maria [VerfasserIn]
Matarrese, Paola [VerfasserIn]
Falchi, Mario [VerfasserIn]
Iosi, Francesca [VerfasserIn]
Raggi, Carla [VerfasserIn]
Parolini, Isabella [VerfasserIn]
Carè, Alessandra [VerfasserIn]
Sargiacomo, Massimo [VerfasserIn]
Gagliardi, Maria Cristina [VerfasserIn]
Fecchi, Katia [VerfasserIn]

Links:

Volltext

Themen:

97C5T2UQ7J
Amphisomes
Autophagy
Caveolin
Caveolin 1
Cell migration
Cholesterol
Endosome
Extracellular vesicles
Journal Article
Melanoma

Anmerkungen:

Date Completed 25.01.2023

Date Revised 01.02.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/tra.12878

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM350319057