BOYE, Kevin; PUJOL, Nadege; ALVES, Isabel; CHEN, Y. P.; DAUBON, Thomas; LEE, Y. Z.; DEDIEU, S.; CONSTANTIN, Marion; BELLO, L.; ROSSI, M.; BJERKVIG, R.; SUE, S. C.; BIKFALVI, Andreas; BILLOTTET, Clotilde

doi:10.1038/s41467-017-01686-y

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BOYE, Kevin
Laboratoire Angiogenèse et Micro-environnement des Cancers [LAMC]

PUJOL, Nadege
Laboratoire Angiogenèse et Micro-environnement des Cancers [LAMC]

ALVES, Isabel

Chimie et Biologie des Membranes et des Nanoobjets [CBMN]

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Nature Communications. 2017-11, vol. 8

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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 CXCR3A 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.< Leer menos

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The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors

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