The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors.
Nat Commun
; 8(1): 1571, 2017 11 17.
Article
em En
| MEDLINE
| ID: mdl-29146996
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Movimento Celular
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Glioblastoma
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Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade
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Receptores CXCR3
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2017
Tipo de documento:
Article