小柯机器人

美国加州大学洛杉矶分校David A. Nathanson和Steven J. Bensinger共同合作，近期取得重要工作进展。他们研究发现CDKN2A 缺失重塑脂质代谢为胶质母细胞瘤引发铁死亡。相关研究成果2023年5月25日在线发表于《癌细胞》杂志上。

据介绍，恶性肿瘤表现出异质性代谢重编程，阻碍了代谢靶向治疗可翻译脆弱性的识别。肿瘤中的分子改变如何促进代谢多样性和不同的靶向依赖性仍不清楚。

研究人员创建了一个由156种分子多样性胶质母细胞瘤（GBM）肿瘤和衍生模型的脂质组学、转录组学和基因组数据组成的资源。通过将GBM脂质体与分子数据集进行综合分析，研究人员确定CDKN2A缺失重塑了GBM脂质，显著地将可氧化的多不饱和脂肪酸重新分布到不同的脂质区室中。因此，CDKN2A缺失的GBM表现出更高的脂质过氧化，选择性地引发肿瘤的脱铁性贫血。

总之，这项研究提供了临床和临床前GBM标本的分子和脂质组学资源，研究人员利用这些资源来检测GBM中复发的分子病变和脂质代谢改变之间的治疗可利用的联系。

附：英文原文

Title: CDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis

Author: Jenna K. Minami, Danielle Morrow, Nicholas A. Bayley, Elizabeth G. Fernandez, Jennifer J. Salinas, Christopher Tse, Henan Zhu, Baolong Su, Rhea Plawat, Anthony Jones, Alessandro Sammarco, Linda M. Liau, Thomas G. Graeber, Kevin J. Williams, Timothy F. Cloughesy, Scott J. Dixon, Steven J. Bensinger, David A. Nathanson

Issue&Volume: 2023-05-25

Abstract: Malignant tumors exhibit heterogeneous metabolic reprogramming, hindering the identification of translatable vulnerabilities for metabolism-targeted therapy. How molecular alterations in tumors promote metabolic diversity and distinct targetable dependencies remains poorly defined. Here we create a resource consisting of lipidomic, transcriptomic, and genomic data from 156 molecularly diverse glioblastoma (GBM) tumors and derivative models. Through integrated analysis of the GBM lipidome with molecular datasets, we identify CDKN2A deletion remodels the GBM lipidome, notably redistributing oxidizable polyunsaturated fatty acids into distinct lipid compartments. Consequently, CDKN2A-deleted GBMs display higher lipid peroxidation, selectively priming tumors for ferroptosis. Together, this study presents a molecular and lipidomic resource of clinical and preclinical GBM specimens, which we leverage to detect a therapeutically exploitable link between a recurring molecular lesion and altered lipid metabolism in GBM.

DOI: 10.1016/j.ccell.2023.05.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00168-X

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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