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

Kevin Boyé, Kevin Boyé, Nadège Pujol, Nadège Pujol, Isabel D Alves, Ya Ping Chen, Thomas Daubon, Thomas Daubon, Thomas Daubon, Thomas Daubon, Yi Zong Lee, Stephane Dedieu, Marion Constantin, Marion Constantin, Lorenzo Bello, Marco Rossi, Rolf Bjerkvig, Rolf Bjerkvig, Shih Che Sue, Andreas BikfalviAndreas Bikfalvi, Clotilde Billottet, Clotilde Billottet

Research output: Contribution to journalArticle

Abstract

© 2017 The Author(s). 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.
Original languageEnglish
Pages (from-to)1571
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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    Boyé, K., Boyé, K., Pujol, N., Pujol, N., D Alves, I., Chen, Y. P., Daubon, T., Daubon, T., Daubon, T., Daubon, T., Lee, Y. Z., Dedieu, S., Constantin, M., Constantin, M., Bello, L., Rossi, M., Bjerkvig, R., Bjerkvig, R., Sue, S. C., ... Billottet, C. (2017). The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors. Nature Communications, 8(1), 1571. https://doi.org/10.1038/s41467-017-01686-y