线粒细胞和化协调特定环境的线粒体质量控制和EMT/MET可塑性,以驱动癌细胞入侵
Bin-Hsu Mao1, Bo-Kai Su2, Ying-Jan Wang3,4
1Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan City, Taiwan.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 17, 2026
概括
线粒体质量控制 (MQC) 集成瘤信号和微环境线索来驱动癌症转移. 准ubiquitin-mitochondria接口可以恢复线粒体的健康并限制癌症的传播.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 转移性侵袭性是由内在的瘤程序和微环境因素驱动的.
- 线粒体质量控制 (MQC) 是这些信号的关键融合点.
- 了解MQC如何适应瘤环境对于癌症进展至关重要.
研究的目的:
- 阐明瘤环境如何塑造线粒体适应和影响转移性行为.
- 确定将线粒体动力学与癌细胞侵入性联系起来的分子机制.
- 探索作为治疗点的乌比奎丁-线粒体接口.
主要方法:
- 分析瘤内在状态 (例如mtROS,mtDNA完整性,表观遗传学,刚性) 和外在景观 (例如氧气,营养,ECM, stromal信号).
- 研究线粒体适应途径,包括生物能学,氧化还原平衡,代谢可塑性,裂变融合和Ca2+恒温.
- 检查对线粒体应激反应中的线粒体活化的检查 (例如,mtDNA妥协,mtUPR).
- 通过E3结合酶和双结合酶对ubiquitin结合的机制研究,将线粒体重塑与细胞骨变化和入侵联系起来.
主要成果:
- 瘤环境决定了线粒体的适应,影响了表皮-介质细胞过渡 (EMT) /介质细胞-表皮细胞过渡 (MET) 的可塑性和癌细胞状态 (迁移性,侵入性,增殖性).
- 线粒体的脆弱性,如mtDNA损害和mtUPR激活,触发线粒体食,以保持在压力下有机体的健康.
- 乌比基信号传递作为一个关键的接口,连接线粒体重塑和线粒体与细胞骨动力学和侵入性表型.
结论:
- 无处不在-线粒体接口是转移性侵袭性的中央调节者.
- 通过像PROTACs或E3结合酶,二维基提纳酶或线粒酶通路调节器等策略,准这种接口,提供了一个有前途的治疗途径.
- 通过这些方法恢复线粒体平衡,可以有效地限制瘤扩散.
相关概念视频
01:13The Proteasome
1.8K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.8K
02:18The Proteasome
10.3K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.3K
01:19Translocation of Proteins into the Mitochondria
13.5K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.5K
01:36Delivery Pathways to the Lysosome
10.3K
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...
10.3K
03:03mTOR Signaling and Cancer Progression
4.9K
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...
4.9K
02:58Regulated Protein Degradation
9.0K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
9.0K