Annexin A6 and NPC1 regulate LDL-inducible cell migration and distribution of focal adhesions.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 01 2022
12 01 2022
Historique:
received:
21
07
2021
accepted:
22
12
2021
entrez:
13
1
2022
pubmed:
14
1
2022
medline:
1
3
2022
Statut:
epublish
Résumé
Cholesterol is considered indispensable for cell motility, but how physiological cholesterol pools enable cells to move forward remains to be clarified. The majority of cells obtain cholesterol from the uptake of Low-Density lipoproteins (LDL) and here we demonstrate that LDL stimulates A431 squamous epithelial carcinoma and Chinese hamster ovary (CHO) cell migration and invasion. LDL also potentiated epidermal growth factor (EGF) -stimulated A431 cell migration as well as A431 invasion in 3-dimensional environments, using organotypic assays. Blocking cholesterol export from late endosomes (LE), using Niemann Pick Type C1 (NPC1) mutant cells, pharmacological NPC1 inhibition or overexpression of the annexin A6 (AnxA6) scaffold protein, compromised LDL-inducible migration and invasion. Nevertheless, NPC1 mutant cells established focal adhesions (FA) that contain activated focal adhesion kinase (pY397FAK, pY861FAK), vinculin and paxillin. Compared to controls, NPC1 mutants display increased FA numbers throughout the cell body, but lack LDL-inducible FA formation at cell edges. Strikingly, AnxA6 depletion in NPC1 mutant cells, which restores late endosomal cholesterol export in these cells, increases their cell motility and association of the cholesterol biosensor D4H with active FAK at cell edges, indicating that AnxA6-regulated transport routes contribute to cholesterol delivery to FA structures, thereby improving NPC1 mutant cell migratory behaviour.
Identifiants
pubmed: 35022465
doi: 10.1038/s41598-021-04584-y
pii: 10.1038/s41598-021-04584-y
pmc: PMC8755831
doi:
Substances chimiques
Annexin A6
0
Carrier Proteins
0
Cholesterol, LDL
0
Membrane Proteins
0
Niemann-Pick C1 Protein
0
STARD3 protein, human
0
rab7 GTP-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
596Informations de copyright
© 2022. The Author(s).
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