Author:

Keywords:

ACTIVATION, ANGIOGENESIS, APELIN, Cell Biology, FAMILY, GAPS, GLIOBLASTOMA STEM-CELLS, GROWTH, GTPASES, IDENTIFICATION, Life Sciences & Biomedicine, PROMOTES TUMORIGENESIS, Science & Technology, ADP-Ribosylation Factors, Aged, Apelin, Apelin Receptors, Biological Transport, Brain Neoplasms, Cell Proliferation, Cytokine Receptor gp130, Endothelial Cells, Female, GTPase-Activating Proteins, Gene Expression Regulation, Neoplastic, Glioblastoma, HEK293 Cells, Humans, Male, Mesenchymal Stem Cells, Neoplastic Stem Cells, Signal Transduction, Spheroids, Cellular, Survival Analysis, Transport Vesicles, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

Abstract:

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.