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功能肝脏基因组学鉴定在癌症恶病质中促进消耗的肝因子
作者:小柯机器人 发布时间:2025/7/22 15:23:21

德国糖尿病和癌症研究所Mauricio Berriel Diaz课题组的最新研究探明了功能肝脏基因组学鉴定在癌症恶病质中促进消耗的肝因子。2025年7月21日,国际知名学术期刊《细胞》发表了这一成果。

该研究团队对各种体重稳定型癌症和癌症恶病质模型的肝脏进行了转录组学和表观基因组学分析。一项综合多水平分析方法确定了一个独特的基因表达特征,其中包括肝细胞分泌因子和生物钟成分REV-ERBα,它们是癌症恶病质中肝脏转录重编程的关键调节剂。值得注意的是,恶病质中REV-ERBα的肝细胞特异性基因重组改善了外周组织的消耗。这种改善与特定恶病质控制的肝细胞分泌因子水平的降低有关。这些肝因子促进多种细胞类型的分解代谢,并在恶病质癌患者中升高。他们的发现揭示了肝脏在癌症恶病质中导致外周组织消耗的机制,为未来的治疗干预提供了前景。

据介绍,在癌症恶病质中,肿瘤的存在会引发全身代谢紊乱,导致患者不由自主的体重减轻和加速死亡。

附:英文原文

Title: Functional liver genomics identifies hepatokines promoting wasting in cancer cachexia

Author: Doris Kaltenecker, Sren Fisker Schmidt, Peter Weber, Anne Loft, Pauline Morigny, Juliano Machado, Julia Geppert, Kerstin Beate Saul, Pia Benedikt, Claudia-Eveline Molocea, Rachel Scott, Kerstin Haase, Marc E. Martignoni, Ana Jimena Alfaro, Kan Kau Chow, Estefania Simoes, José Pinhata Otoch, Joanna D.C.C. Lima, Charles Swanton, Nadine Spielmann, Martin Hrabé de Angelis, Markus Elsner, Ali Ertürk, Kenneth A. Dyar, Maria Rohm, Olga Prokopchuk, Mariam Jamal-Hanjani, Marilia Seelaender, Johannes Backs, Stephan Herzig, Mauricio Berriel Diaz

Issue&Volume: 2025-07-21

Abstract: In cancer cachexia, the presence of a tumor triggers systemic metabolic disruption that leads to involuntary body weight loss and accelerated mortality in affected patients. Here, we conducted transcriptomic and epigenomic profiling of the liver in various weight-stable cancer and cancer cachexia models. An integrative multilevel analysis approach identified a distinct gene expression signature that included hepatocyte-secreted factors and the circadian clock component REV-ERBα as key modulator of hepatic transcriptional reprogramming in cancer cachexia. Notably, hepatocyte-specific genetic reconstitution of REV-ERBα in cachexia ameliorated peripheral tissue wasting. This improvement was associated with decreased levels of specific cachexia-controlled hepatocyte-secreted factors. These hepatokines promoted catabolism in multiple cell types and were elevated in cachectic cancer patients. Our findings reveal a mechanism by which the liver contributes to peripheral tissue wasting in cancer cachexia, offering perspectives for future therapeutic interventions.

DOI: 10.1016/j.cell.2025.06.039

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00741-X

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:66.85
官方网址:https://www.cell.com/