The glycoprotein GP130 governs the surface presentation of the G protein-coupled receptor APLNR

• Published in: The Journal of cell biology Vol. 220; no. 9; p. 1
• Main Authors: Trillet, Kilian, Jacobs, Kathryn A, André-Grégoire, Gwennan, Thys, An, Maghe, Clément, Cruard, Jonathan, Minvielle, Stéphane, Diest, Sara Gonzalez, Montagnac, Guillaume, Bidère, Nicolas, Gavard, Julie
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 06.09.2021
• Subjects: ADP-Ribosylation Factors - genetics; ADP-Ribosylation Factors - metabolism; Aged; Apelin - genetics; Apelin - metabolism; Apelin Receptors - genetics; Apelin Receptors - metabolism; Arbitration; Biological Transport; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Cancer; Cell Proliferation; Cell self-renewal; Cytokine Receptor gp130 - genetics; Cytokine Receptor gp130 - metabolism; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - mortality; Glioblastoma - pathology; Glycoprotein gp130; Glycoproteins; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; HEK293 Cells; Humans; Life Sciences; Male; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Proteins; Receptors; Signal Transduction; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Stem cells; Stroma; Survival Analysis; Trafficking; Transport Vesicles - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.202004114

Glioblastoma is one of the most lethal forms of adult cancer, with a median survival of ∼15 mo. Targeting glioblastoma stem-like cells (GSCs) at the origin of tumor formation and relapse may prove beneficial. In situ, GSCs are nested within the vascular bed in tight interaction with brain endothelial cells, which positively control their expansion. Because GSCs are notably addicted to apelin (APLN), sourced from the surrounding endothelial stroma, the APLN/APLNR nexus has emerged as a druggable network. However, how this signaling axis operates in gliomagenesis remains underestimated. Here, we find that the glycoprotein GP130 interacts with APLNR at the plasma membrane of GSCs and arbitrates its availability at the surface via ELMOD1, which may further impact on ARF-mediated endovesicular trafficking. From a functional standpoint, interfering with GP130 thwarts APLNR-mediated self-renewal of GSCs ex vivo. Thus, GP130 emerges as an unexpected cicerone to the G protein-coupled APLN receptor, opening new therapeutic perspectives toward the targeting of cancer stem cells.