Rac1b和活性氧物种介导MMP-3诱导的EMT和基因组不稳定性
Derek C Radisky1, Dinah D Levy, Laurie E Littlepage
1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. dcradisky@lbl.gov
Nature
|July 8, 2005
概括
瘤微环境中的斯特罗梅利辛-1 (MMP-3) 驱动乳腺癌的进展. MMP-3触发了活性氧物种 (ROS) 和基因组不稳定性,导致恶性转变.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 瘤微环境 (TME) 可以促进癌症的进展和瘤的形成.
- 斯特罗梅林素-1/矩阵金属蛋白酶-3 (MMP-3),一种 stromal 酶,在乳腺瘤中被上调.
- 之前的研究表明,MMP-3诱导了上皮层-介质细胞过渡 (EMT) 和恶性转变.
研究的目的:
- 阐明通过MMP-3促进恶性转变的分子途径.
- 确定MMP-3在乳腺瘤微环境中的细胞和组织结构改变中的作用.
主要方法:
- 对小鼠乳腺上皮细胞暴露于MMP-3.
- 对基因表达的分析,包括替代拼接的Rac1和Snail.
- 评估活性氧物种 (ROS) 水平和DNA氧化损伤.
- 评估乳腺癌中的基因组不稳定性.
主要成果:
- 暴露于MMP-3诱导了Rac1的替代拼接形式,增加了细胞ROS.
- 增加的ROS刺激了牛的表情和EMT.
- 暴露于MMP-3导致氧化DNA损伤和基因组不稳定.
- 这些分子事件与 in vitro 和 in vivo 的恶性转变相关.
结论:
- MMP-3启动了一条新的途径,将乳腺TME与恶性转变联系起来.
- 由MMP-3诱导的ROS和基因组不稳定性是推动癌症进展的关键机制.
- 向MMP-3可能为乳腺癌提供治疗策略.
相关概念视频
Mismatch Repair
38.2K
Overview
38.2K
Nucleotide Excision Repair
33.7K
Overview
33.7K
Nucleotide Excision Repair
4.7K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
4.7K
Mismatch Repair
5.4K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.4K
MAPK Signaling Cascades
7.3K
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...
7.3K
Role of Matrix Metalloproteases in Degradation of ECM
2.9K
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.9K


