ArticleScientific reports2022
Annexin A6 and NPC1 regulate LDL-inducible cell migration and distribution of focal adhesions.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Cholesterol homeostasis and cancer: a new perspective on the low-density lipoprotein receptor.Cellular oncology (Dordrecht, Netherlands) · 2022Pooled it
- Small Molecules to Elevate Rab7-GTPase Activity and Lower Cholesterol Accumulation in Niemann-Pick Type C Disease.Pharmaceutical research · 2026Article
- NPC1 promotes the progression of hepatocellular carcinoma by mediating the accumulation of neutrophils into the tumor microenvironment.FEBS open bio · 2025Article
- Chikungunya Replication and Infection Is Dependent upon and Alters Cellular Hexosylceramide Levels in Vero Cells.Viruses · 2025Article
- Lysosome-Mitochondrial Crosstalk in Cellular Stress and Disease.Antioxidants (Basel, Switzerland) · 2025Review
- NPC1 controls TGFBR1 stability in a cholesterol transport-independent manner and promotes hepatocellular carcinoma progression.Nature communications · 2025Article
- ANXA6: a key molecular player in cancer progression and drug resistance.Discover oncology · 2023Review
- Cholesterol and Sphingomyelin Polarize at the Leading Edge of Migrating Myoblasts and Involve Their Clustering in Submicrometric Domains.Biomolecules · 2023Article
- CaAdvances in experimental medicine and biology · 2023Article
- AnnexinA6: a potential therapeutic target gene for extracellular matrix mineralization.Frontiers in cell and developmental biology · 2023Review
- Fluid Shear Stress Regulates Osteogenic Differentiation via AnnexinA6-Mediated Autophagy in MC3T3-E1 Cells.International journal of molecular sciences · 2022Article
- Article
- Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance.International journal of molecular sciences · 2022Review
- Pathobiological functions and clinical implications of annexin dysregulation in human cancers.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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