失去Myo19会通过增强微环境ROS梯度和化学反应来增加转移
Xiaoyu Ren1, Peng Shi2,3, Jing Su4
1Institute of Systems Biomedicine, Peking University Health Science Center, Key Laboratory of Tumor Systems Biology, Beijing, 100191, China.
EMBO reports
|January 26, 2024
概括
过氧化 (H2O2) 作为化学吸引剂,在转移过程中引导瘤细胞. 失去了Myosin 19 (Myo19) 蛋白质会破坏线粒体,增强这种效果并促进癌症的扩散.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 瘤转移涉及受化学信号影响的定向细胞迁移.
- 过氧化 (H2O2) 是一种已知的中性粒细胞化学吸引剂,但其在瘤细胞扩散中的作用尚不清楚.
- 在瘤微环境中反应性氧物种 (ROS) 的空间分布尚不清楚.
研究的目的:
- 为了研究ROS在3D瘤球体中的空间分布.
- 确定H2O2梯度在瘤细胞化学反应和转移中的作用.
- 探索线粒体和Myosin 19 (Myo19) 在调节ROS梯度和瘤扩散中的功能.
主要方法:
- 用3D瘤球形模型来分析ROS分布.
- 进行了化疗试验,以评估瘤细胞迁移的反应H2O2梯度.
- 研究了涉及Src和RhoA的分子通路.
- 研究了线粒体和Myo19在ROS产生和瘤细胞传播中的作用.
主要成果:
- 在3D瘤球形和瘤微环境的外围确定了ROS度梯度,特别是H2O2.
- H2O2梯度通过激活Src和抑制RhoA来诱导瘤细胞化学反应.
- 缺少线粒体晶体重塑蛋白质,如Myo19,增强ROS梯度,促进瘤扩散.
- 在体内,myo19的下调与瘤转移的增加有关.
结论:
- 瘤微环境中的ROS,特别是H2O2,可以作为瘤细胞的化学吸引剂.
- 线粒体功能障碍,特别是由于Myo19等蛋白质导致的形重塑受损,可以增强ROS梯度,促进瘤入侵和转移.
- 在各种瘤中观察到myo19的下调,并且与转移负相关,表明其作为治疗点的潜力.
相关概念视频
The Tumor Microenvironment
6.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.6K
Metastasis
5.5K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.5K
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
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
Chemotaxis and Direction of Cell Migration
3.4K
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
3.4K


