线粒体Ca2+道MCU对于瘤生长至关重要,因为它支持细胞周期的进展和增殖
Emily Fernandez Garcia1, Usha Paudel1, Michael C Noji2,3
1Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Frontiers in cell and developmental biology
|June 26, 2023
概括
线粒体通过线粒体单载体 (MCU) 吸收线粒体对于癌细胞增殖和瘤发生至关重要. 删除MCU通过改变细胞代谢和信号来抑制瘤生长,突出显示MCU作为治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 癌症研究 癌症研究
背景情况:
- 线粒体单载体 (MCU) 促进线粒体Ca2+吸收,影响细胞生物能和TCA循环.
- 虽然MCU影响癌细胞增殖,但由于有限的遗传模型,其在瘤发生中的确切作用仍然不清楚.
研究的目的:
- 调查MCU介导的Ca2+流入在癌细胞增殖和瘤形成中的作用.
- 阐明MCU缺失在癌细胞中的代谢和信号后果.
主要方法:
- 在转变的小鼠纤维细胞和HEK293T细胞中遗传删除MCU.
- 在体外测试扩散,入侵,球形形成和细胞循环进展.
- 使用小鼠异种移植模型进行体内研究.
- 分析线粒体的生物能量学,包括Ca2+度,膜潜力,呼吸和代谢流量 (葡萄糖和谷氨酸的利用).
主要成果:
- 在异种移植模型中,MCU删除抑制了瘤生长,减少了增殖和延迟细胞周期进展.
- 缺乏MCU会影响癌症干细胞类球状体的形成和侵入.
- 奇怪的是,线粒体的生物能量 (矩阵Ca2+,膜潜力,呼吸) 没有受到MCU删除的影响.
- MCU 除增加了糖解和谷氨醇解,使细胞对营养限制敏感,并改变了细胞质Ca2+ 信号传递.
结论:
- 瘤发生取决于MCU,这对于细胞代谢和扩散所需的Ca2+动态至关重要.
- 在调节癌细胞代谢灵活性和Ca2+信号通路方面,MCU起着至关重要的作用.
- 向MCU为癌症治疗提供了一个潜在的治疗策略.
相关概念视频
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
Electron Transport Chain: Complex I and II
14.6K
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...
ROS generation is regulated and maintained at moderate levels necessary...
14.6K
Mitogens and the Cell Cycle
6.6K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
Adaptive Mechanisms in Cancer Cells
5.8K
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,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
M-Cdk Drives Transition Into Mitosis
5.6K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.6K
Tumor Progression
6.4K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.4K


