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] |
---|
Links: |
---|
Themen: |
97C5T2UQ7J |
---|
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 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM350319057 | ||
003 | DE-627 | ||
005 | 20231226044729.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1111/tra.12878 |2 doi | |
028 | 5 | 2 | |a pubmed24n1167.xml |
035 | |a (DE-627)NLM350319057 | ||
035 | |a (NLM)36519961 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Peruzzu, Daniela |e verfasserin |4 aut | |
245 | 1 | 0 | |a Inhibition of cholesterol transport impairs Cav-1 trafficking and small extracellular vesicles secretion, promoting amphisome formation in melanoma cells |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 25.01.2023 | ||
500 | |a Date Revised 01.02.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023 The Authors. Traffic published by John Wiley & Sons Ltd. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a amphisomes | |
650 | 4 | |a autophagy | |
650 | 4 | |a caveolin | |
650 | 4 | |a cell migration | |
650 | 4 | |a cholesterol | |
650 | 4 | |a endosome | |
650 | 4 | |a extracellular vesicles | |
650 | 4 | |a melanoma | |
650 | 7 | |a Caveolin 1 |2 NLM | |
650 | 7 | |a Cholesterol |2 NLM | |
650 | 7 | |a 97C5T2UQ7J |2 NLM | |
700 | 1 | |a Boussadia, Zaira |e verfasserin |4 aut | |
700 | 1 | |a Fratini, Federica |e verfasserin |4 aut | |
700 | 1 | |a Spadaro, Francesca |e verfasserin |4 aut | |
700 | 1 | |a Bertuccini, Lucia |e verfasserin |4 aut | |
700 | 1 | |a Sanchez, Massimo |e verfasserin |4 aut | |
700 | 1 | |a Carollo, Maria |e verfasserin |4 aut | |
700 | 1 | |a Matarrese, Paola |e verfasserin |4 aut | |
700 | 1 | |a Falchi, Mario |e verfasserin |4 aut | |
700 | 1 | |a Iosi, Francesca |e verfasserin |4 aut | |
700 | 1 | |a Raggi, Carla |e verfasserin |4 aut | |
700 | 1 | |a Parolini, Isabella |e verfasserin |4 aut | |
700 | 1 | |a Carè, Alessandra |e verfasserin |4 aut | |
700 | 1 | |a Sargiacomo, Massimo |e verfasserin |4 aut | |
700 | 1 | |a Gagliardi, Maria Cristina |e verfasserin |4 aut | |
700 | 1 | |a Fecchi, Katia |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Traffic (Copenhagen, Denmark) |d 2000 |g 24(2023), 2 vom: 10. Feb., Seite 76-94 |w (DE-627)NLM111198879 |x 1600-0854 |7 nnns |
773 | 1 | 8 | |g volume:24 |g year:2023 |g number:2 |g day:10 |g month:02 |g pages:76-94 |
856 | 4 | 0 | |u http://dx.doi.org/10.1111/tra.12878 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 24 |j 2023 |e 2 |b 10 |c 02 |h 76-94 |