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Article Dans Une Revue Journal of Cell Biology Année : 2021

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

Résumé

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.
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Origine : Publication financée par une institution

Dates et versions

inserm-03340113 , version 1 (10-09-2021)

Identifiants

Citer

Kilian Trillet, Kathryn Jacobs, Gwennan André-Grégoire, An Thys, Clément Maghe, et al.. The glycoprotein GP130 governs the surface presentation of the G protein–coupled receptor APLNR. Journal of Cell Biology, 2021, 220 (9), pp.e202004114. ⟨10.1083/jcb.202004114⟩. ⟨inserm-03340113⟩
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