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.

中文翻译：

---

糖蛋白 GP130 控制 G 蛋白偶联受体 APLNR 的表面呈现

胶质母细胞瘤是最致命的成人癌症之一，中位生存期约为 15 个月。在肿瘤形成和复发的起源处靶向胶质母细胞瘤干样细胞（GSC）可能是有益的。在原位，GSC 嵌套在血管床内，与脑内皮细胞紧密相互作用，从而积极控制它们的扩张。由于 GSC 对源自周围内皮基质的 apelin (APLN) 特别上瘾，因此 APLN/APLNR 关系已成为可药物网络。然而，该信号轴在神经胶质瘤发生中的运作方式仍然被低估。在这里，我们发现糖蛋白 GP130 与 GSC 质膜上的 APLNR 相互作用，并通过 ELMOD1 仲裁其在表面的可用性，这可能进一步影响 ARF 介导的囊内运输。从功能角度来看，干扰 GP130 会阻碍 APLNR 介导的 GSC 离体自我更新。因此，GP130 作为 G 蛋白偶联 APLN 受体的意想不到的抑制剂而出现，为靶向癌症干细胞开辟了新的治疗前景。