The diffuse nature of Glioblastoma (GBM) tumors poses a challenge to current therapeutic options. We have previously shown that Acyl-CoA Binding Protein (ACBP, also known as DBI) regulates lipid metabolism in GBM cells, favoring fatty acid oxidation (FAO). Here we show that ACBP downregulation results in wide transcriptional changes affecting invasion-related genes. In vivo experiments using patient-derived xenografts combined with in vitro models demonstrated that ACBP sustains GBM invasion via binding to fatty acyl-CoAs. Blocking FAO mimics ACBP^KD-induced immobility, a cellular phenotype that can be rescued by increasing FAO rates. Further investigation into ACBP-downstream pathways served to identify Integrin beta-1, a gene downregulated upon inhibition of either ACBP expression or FAO rates, as a mediator for ACBP’s role in GBM invasion. Altogether, our findings highlight a role for FAO in GBM invasion and reveal ACBP as a therapeutic vulnerability to stall FAO and subsequent cell invasion in GBM tumors.

胶质母细胞瘤 (GBM) 肿瘤的弥漫性对当前的治疗选择提出了挑战。我们之前已经表明，酰基辅酶 A 结合蛋白（ACBP，也称为 DBI）调节 GBM 细胞中的脂质代谢，有利于脂肪酸氧化（FAO）。在这里，我们表明 ACBP 下调导致影响入侵相关基因的广泛转录变化。使用源自患者的异种移植物与体外模型相结合的体内实验表明，ACBP 通过与脂酰辅酶 A 结合来维持 GBM 入侵。阻止粮农组织模仿 ACBP ^KD-诱导不动，一种细胞表型，可以通过提高 FAO 率来挽救。对 ACBP 下游通路的进一步调查有助于确定整合素 beta-1，这是一种在抑制 ACBP 表达或 FAO 率时下调的基因，作为 ACBP 在 GBM 入侵中的作用的中介。总而言之，我们的研究结果强调了 FAO 在 GBM 侵袭中的作用，并揭示了 ACBP 作为一种治疗漏洞，可以阻止 FAO 和随后的 GBM 肿瘤细胞侵袭。