The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2017

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

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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.

Dates and versions

hal-03453986 , version 1 (29-11-2021)

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Kevin Boyé, Nadège Pujol, Isabel D Alves, Ya-Ping Chen, Thomas Daubon, et al.. The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors. Nature Communications, 2017, 8 (1), ⟨10.1038/s41467-017-01686-y⟩. ⟨hal-03453986⟩
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