通过增加氨酸生物合成,UDP-葡萄糖脱酶支持自缺乏的PDAC生长
Minghe Fan1, Sihan Huo1, Yuyao Guo1
1Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, State Key Laboratory of Molecular Oncology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking University International Cancer Institute, Peking University Health Science Center, Beijing 100191, China.
Cell reports
|February 17, 2024
概括
胰腺癌细胞通过降解UDP-葡萄糖脱酶 (UGDH) 而没有自生长. UGDH的积累促进了氨酸 (HA) 合成,推动了增殖. 向HA合成可以治疗胰腺管道腺癌 (PDAC).
科学领域:
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
- 生物化学 生物化学
背景情况:
- 自对于细胞平衡至关重要,但胰腺管腺癌 (PDAC) 可以绕过自抑制的生长.
- 在营养缺乏的情况下,使自性缺陷PDAC存活的机制尚不清楚.
研究的目的:
- 为了阐明在营养缺乏期间自性缺陷PDAC细胞繁殖的机制.
- 研究UDP-葡萄糖脱酶 (UGDH) 和氨酸 (HA) 合成在压力下PDAC生长中的作用.
主要方法:
- 在缺乏营养的PDAC细胞中研究了UGDH降解对序列1 (p62) 的依赖性.
- 评估了积累的UGDH对于PDAC细胞增殖和HA合成的必要性.
- 利用一个正极形小鼠模型来评估向UGDH和HA合成的治疗潜力.
主要成果:
- 营养缺乏导致PDAC中的p62-依赖的UGDH降解.
- 累积的UGDH对于自缺乏的PDAC增殖是必不可少的,因为它在能量剥夺期间增强了HA合成.
- 在PDAC小鼠模型中,通过UGDH向减少瘤重量来抑制HA合成.
结论:
- 自缺乏的PDAC细胞依靠UGDH积累和随后的HA合成在营养压力下进行增殖.
- 向UGDH和抑制HA合成是胰腺癌的潜在治疗策略.
- 联合抑制HA合成和自可能为PDAC提供一种新的治疗方法.
相关概念视频
Autophagy
4.2K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K
Lysosomal Hydrolases
3.8K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.8K
Delivery Pathways to the Lysosome
6.5K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.5K
mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
Autophagic Cell Death
3.4K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K


