文章：

氟苯脲诱导的子宫内膜癌细胞线粒体呼吸抑制与代谢重编程

Forchlorfenuron-Induced Mitochondrial Respiration Inhibition and Metabolic Shifts in Endometrial Cancer

原文发布日期：28 February 2024

DOI: 10.3390/cancers16050976

类型: Article

开放获取: 是

英文摘要：

Forchlorfenuron (FCF) is a widely used plant cytokinin that enhances fruit quality and size in agriculture. It also serves as a crucial pharmacological tool for the inhibition of septins. However, the precise target of FCF has not yet been fully determined. This study reveals a novel target of FCF and elucidates its downstream signaling events. FCF significantly impairs mitochondrial respiration and mediates metabolic shift toward glycolysis, thus making cells more vulnerable to glycolysis inhibition. Interestingly, FCF’s impact on mitochondrial function persists, even in cells lacking septins. Furthermore, the impaired mitochondrial function leads to the degradation of HIF-1α, facilitated by increased cellular oxygen. FCF also induces AMPK activation, suppresses Erk1/2 phosphorylation, and reduces the expression of HER2, β-catenin, and PD-L1. Endometrial cancer is characterized by metabolic disorders such as diabetes and aberrant HER2/Ras-Erk1/2/β-catenin signaling. Thus, FCF may hold promise as a potential therapeutic in endometrial cancer.

摘要翻译： 

氯吡脲（FCF）是一种广泛应用于农业的植物细胞分裂素，可提高果实品质和增大果实体积。同时，它也是抑制septin蛋白的关键药理学工具。然而，FCF的确切作用靶点尚未完全明确。本研究揭示了FCF的一个新靶点，并阐明了其下游信号传导事件。FCF显著损害线粒体呼吸功能，促使细胞代谢向糖酵解途径转变，从而使细胞对糖酵解抑制更为敏感。值得注意的是，即使在缺乏septin蛋白的细胞中，FCF对线粒体功能的影响依然持续存在。此外，受损的线粒体功能导致细胞氧含量增加，进而促进HIF-1α降解。FCF还能诱导AMPK活化，抑制Erk1/2磷酸化，并降低HER2、β-catenin和PD-L1的表达。子宫内膜癌的特征包括糖尿病等代谢紊乱以及异常的HER2/Ras-Erk1/2/β-catenin信号传导。因此，FCF有望成为子宫内膜癌的潜在治疗药物。

原文链接：

Forchlorfenuron-Induced Mitochondrial Respiration Inhibition and Metabolic Shifts in Endometrial Cancer