Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Low-density lipoprotein (LDL)-cholesterol delivery from late endosomes to the plasma membrane regulates focal adhesion dynamics and cell migration, but the mechanisms controlling it are poorly characterized. Here, we employed auxin-inducible rapid degradation of oxysterol-binding protein-related protein 2 (ORP2/OSBPL2) to show that endogenous ORP2 mediates the transfer of LDL-derived cholesterol from late endosomes to focal adhesion kinase (FAK)-/integrin-positive recycling endosomes in human cells. In vitro, cholesterol enhances membrane association of FAK to PI(4,5)P -containing lipid bilayers. In cells, ORP2 stimulates FAK activation and PI(4,5)P generation in endomembranes, enhancing cell adhesion. Moreover, ORP2 increases PI(4,5)P in NPC1-containing late endosomes in a FAK-dependent manner, controlling their tubulovesicular trafficking. Together, these results provide evidence that ORP2 controls FAK activation and LDL-cholesterol plasma membrane delivery by promoting bidirectional cholesterol/PI(4,5)P exchange between late and recycling endosomes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281050 | PMC |
| http://dx.doi.org/10.15252/embj.2020106871 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Vitamin D Binding Protein, a Ligand of Integrin beta 1, Motivates Both Tumor Cells and Schwann Cells to Promote Perineural Invasion in Pancreatic Ductal Adenocarcinoma.
Adv Sci (Weinh)
September 2025
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
Perineural invasion (PNI) is a common pathological characteristic of pancreatic ductal adenocarcinoma (PDAC), closely linked to postoperative recurrence, metastasis, and unfavorable prognosis. Nevertheless, the precise mechanisms that govern PNI in PDAC remain poorly elucidated. Here, group-specific component protein (GC) is identified as one of the most significantly upregulated genes related to PNI, primarily derived from malignant ductal cells compared to other cell types.
View Article and Find Full Text PDFMultivalent DNA Origami Enables Single-Molecule Dissection of Integrin αvβ6-Receptor Tyrosine Kinase Crosstalk in Cancer Biology.
ACS Nano
September 2025
Department of Chemistry, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom.
Nanoscale organization of integrin-mediated receptor crosstalk is crucial for controlling cellular signaling in cancer biology. Previously, interactions between integrin αvβ6 and receptor tyrosine kinases (RTKs) have been implicated in cancer progression, but the spatial regulatory mechanisms remain undefined. Here, we developed a programmable DNA origami-based platform for nanoscale control of heteroligand multivalency and spacing, enabling systematic investigation of αvβ6-RTK interactions in cancer biology.
View Article and Find Full Text PDFDesign, synthesis and biological evaluation of triazolo[1,5-a]pyrimidine derivatives as new antiproliferative agents with multikinase inhibitory activity.
Bioorg Chem
August 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, P.O. Box 11566, Abbassia, Cairo, Egypt. Electronic address:
Two series of triazolo[1,5-a]pyrimidines were designed and synthesized as antiproliferative agents targeting multi kinase inhibition aiming to increase potency and combat drug resistance. The synthesized compounds were tested for their antiproliferative activity. The triazolopyrimidine derivatives 9b, 9c, 12b and 12c showed promising anticancer activities, in particular, compounds 12b and 12c displayed broad spectrum antiproliferative potential against NCI cancer cell lines with GI mean value of 10.
View Article and Find Full Text PDFCyclic Heptapeptide FZ1 Acts as an Integrin αvβ3 Agonist to Facilitate Diabetic Skin Wound Healing by Enhancing Angiogenesis.
J Med Chem
September 2025
Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China.
Diabetic wound healing remains a persistent clinical challenge, necessitating the development of effective therapeutic agents and a deeper understanding of regulatory mechanisms. The cyclic heptapeptide FZ1, characterized by favorable biocompatibility, exhibited significantly greater efficacy than rh-bFGF and Cy in promoting cell proliferation and migration. In diabetic wound models, FZ1 markedly accelerated tissue regeneration and stimulated angiogenesis, as indicated by the upregulation of CD31 and α-SMA.
View Article and Find Full Text PDFObjective- Surgically created upper extremity arteriovenous fistulae (AVF) are the preferred vascular access for patients requiring dialysis. It is estimated, however, that 50% of AVF fail within one year due to aggressive neointimal hyperplasia, which significantly increases morbidity and mortality. Matrix metalloproteinase-3 (MMP-3), also known as stromelysin-1, is a member of the metalloproteinase family that plays a critical role in the pathogenesis of many human disorders by degrading extracellular matrix and regulating molecular signaling pathways.
View Article and Find Full Text PDF