相关实验视频

Updated: Sep 9, 2025

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Published on: August 31, 2022

RAB5核酸结合促进乙氧化燃料肝细胞癌细胞增殖

Kelly O Otakhor¹, Mohd Ali Abbas Zaidi², Rebecca Oberley-Deegan²

¹Department of Molecular Genetics and Cell Biology, University of Nebraska Medical Center, Omaha, NE.

bioRxiv : the preprint server for biology

|September 2, 2025

概括

Rab5 GTPase 调节肝癌细胞中的脂质滴动力学. 它的活性对脂质分解,线粒体能量产生和肝细胞癌 (HCC) 细胞增殖至关重要,为其提供了潜在的治疗点.

科学领域:

细胞生物学
癌症新陈代谢
分子机制

背景情况:

脂质代谢变化和脂质液滴 (LD) 动态是肝细胞癌 (HCC) 的特征.
在HCC细胞中LD流通和代谢的分子调节尚未完全理解.
小GTPase Rab5对LDs的局部化表明它可能在LD转换中发挥作用.

研究的目的:

研究Rab5在HCC细胞中调节LD稳态中的作用.
阐明Rab5对HCC细胞增殖和代谢的影响.
探索Rab5-LD相互作用的调节.

主要方法:

使用Rab5活跃 (Q79L) 和不活跃 (S34N) 突变来研究LD相关性.
在营养饥饿条件下研究了Rab5的GTP加载和LD招募.
评估Rab5抑制对LD代谢,线粒体呼吸和HCC细胞增殖的影响.
对HCC患者样本进行了转录组分析.

主要成果:

与不活跃的Rab5相比,活跃的Rab5与LD的相关性增加.
营养饥饿增强了Rab5的GTP加载和LD招募.
抑制Rab5的GTP结合会影响LD代谢,减少线粒体的氧化酸化,并阻碍HCC细胞的增殖.
在HCC患者样本中发现RAB5过度表达,与生存率较低相关.

结论:

Rab5 的 GTPase 循环对 HCC 细胞的 LD 动态进行了关键调节.
Rab5 控制了 LD 循环,以支持线粒体的能量产生和癌细胞的增殖.
针对Rab5介导的LD代谢是一种新的治疗策略.

关键词:

肝细胞癌细胞内贩运脂质滴脂肪消化症线粒体新陈代谢拉巴5 脂质新陈代谢

更多相关视频

Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes

Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes

Published on: September 9, 2021

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

相关概念视频

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

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...

Electron Transport Chain: Complex I and II

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

The Ras Gene

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...

Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...

MAPK Signaling Cascades

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...