2019年8月出版的《细胞—代谢》发表了德国科学家的一项最新研究成果。来自德国癌症研究中心的Julieta Alfonso研究组发现乙酰辅酶A结合蛋白通过维持脂肪酸氧化促进胶质母细胞瘤的发生。

研究人员发现，神经干细胞促增殖因子乙酰辅酶A结合蛋白（ACBP，又称DBI）在GBM中高度表达，通过与乙酰辅酶A结合，其在多个临床前模型中维持细胞高增殖率，促进肿瘤生长，并降低生存率。利用ACBP-乙酰辅酶A结合亲和力变体以及FAO药理调节剂的机制性实验表明，ACBP通过控制长链脂肪乙酰辅酶A在线粒体的使用促进了GBM中的脂肪酸氧化，从而促进肿瘤生长。因此，他们的发现揭示了ACBP建立的脂质代谢与GBM进展之间的关键联系，并提供了一种有效抗GBM增殖代谢的潜在治疗策略。

据悉，多形性胶质母细胞瘤（GBM）经过代谢重编程，以满足肿瘤细胞对ATP和合成代谢的高需求。然而，脂肪酸氧化（FAO）及其调节因子在GBM中的作用在很大程度上是未知的。

附：英文原文

Title: Acyl-CoA-Binding Protein Drives Glioblastoma Tumorigenesis by Sustaining Fatty Acid Oxidation

Author: Ceren Duman, Kaneschka Yaqubi, Angelika Hoffmann, Azer Aylin Acikgz, Andrey Korshunov, Martin Bendszus, Christel Herold-Mende, Hai-Kun Liu, Julieta Alfonso

Issue&Volume:  Volume 30 Issue 2

Abstract: Glioblastoma multiforme (GBM) undergoes metabolic reprogramming to meet the high ATP and anabolic demands of the tumor cells. However, the role of fatty acid oxidation (FAO) and its regulators in the GBM context has been largely unknown. Here, we show that the neural stem cell pro-proliferative factor acyl-CoA-binding protein (ACBP, also known as DBI) is highly expressed in GBM, and by binding to acyl-CoAs, it cell-autonomously maintains high proliferation rates, promoting tumor growth and poor survival in several preclinical models. Mechanistic experiments using ACBP-acyl-CoA binding affinity variants and pharmacological FAO modulators suggest that ACBP supports tumor growth by controlling the availability of long-chain fatty acyl-CoAs to mitochondria, promoting FAO in GBM. Thus, our findings uncover a critical link between lipid metabolism and GBM progression established by ACBP and offer a potential therapeutic strategy for an effective anti-proliferative metabolic management of GBM.

DOI: https://doi.org/10.1016/j.cmet.2019.04.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30188-3