通过诱导替代性脂质吸收和促进胆固醇运输,mTOR抑制重新编程细胞脂质稳态
Sejeong Shin1, Min-Joon Han2, Ishika Patel3
1Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Molecular cell
|September 19, 2025
概括
拉巴胺素 (mTOR) 抑制的机械标重编程癌细胞脂质代谢. 这涉及增加低密度脂蛋白受体相关蛋白6 (LRP6) 和尼曼-皮克C1 (NPC1) 活性,为癌症治疗提供了新的治疗点.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 拉巴胺素 (mTOR) 途径的机械性标关键调节细胞脂质平衡.
- mTOR和脂质代谢的失调与各种疾病有关,特别是癌症.
- 了解mTOR在重编程脂质代谢中的作用对于治疗的发展至关重要.
研究的目的:
- 阐明mTOR抑制改变癌细胞中的脂质稳态的机制.
- 确定参与mTOR介导的脂质重编程的关键分子参与者.
- 评估在癌症模型中准这些途径的治疗潜力.
主要方法:
- 利用人类癌细胞系研究mTOR抑制对脂质代谢的影响.
- 研究了真核启动因子3D (eIF3D),低密度脂蛋白受体相关蛋白6 (LRP6),肝X受体β (LXRβ) 和尼曼-皮克疾病型C (NPC) 细胞内胆固醇载体1 (NPC1) 的作用.
- 采用老鼠异种移植模型来评估结合mTOR抑制与LRP6或NPC1向的治疗疗效.
主要成果:
- 在癌细胞中的mTOR抑制通过eIF3D上调LRP6,增强脂质吸收.
- 激活的LXRβ促进胆固醇从溶解体到血的运输,由NPC1.1促进.
- 结合的mTOR抑制与LRP6淘汰或NPC1向显著抑制瘤生长 in vivo.
结论:
- 在癌症进展过程中,mTOR信号在重编程脂质平衡中起着至关重要的反作用.
- 针对已识别的脂质代谢途径 (LRP6,NPC1) 与mTOR抑制一起,是一个有前途的治疗策略.
- 这些发现为异常mTOR信号传递和脂质失调的疾病提供了潜在的治疗方法.
相关概念视频
mTOR Signaling and Cancer Progression
4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.6K
PI3K/mTOR/AKT Signaling Pathway
5.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.4K
Cholesterol: Significance and Regulation
1.2K
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
1.2K
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
1.3K
Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
1.3K
Lipid Catabolism
862
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
862
Receptor-mediated Endocytosis
110.5K
Overview
110.5K


