The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29146996.
- Also identified by DOI 10.1038/s41467-017-01686-y and PMC identifier 5691136.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
CXCR3 plays important roles in angiogenesis, inflammation, and cancer. However, the precise mechanism of regulation and activity in tumors is not well known. We focused on CXCR3-A conformation and on the mechanisms controlling its activity and trafficking and investigated the role of CXCR3/LRP1 cross talk in tumor cell invasion. Here we report that agonist stimulation induces an anisotropic response with conformational changes of CXCR3-A along its longitudinal axis. CXCR3-A is internalized via clathrin-coated vesicles and recycled by retrograde trafficking. We demonstrate that CXCR3-A interacts with LRP1. Silencing of LRP1 leads to an increase in the magnitude of ligand-induced conformational change with CXCR3-A focalized at the cell membrane, leading to a sustained receptor activity and an increase in tumor cell migration. This was validated in patient-derived glioma cells and patient samples. Our study defines LRP1 as a regulator of CXCR3, which may have important consequences for tumor biology.
Medical subject headings
- Brain Neoplasms
- Cell Movement
- Glioblastoma
- Low Density Lipoprotein Receptor-Related Protein-1
- Receptors, CXCR3