致病性线粒体DNA突变抑制黑色素瘤转移
Spencer D Shelton1, Sara House1, Vijayashree Ramesh1
1Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390 USA.
bioRxiv : the preprint server for biology
|September 21, 2023
概括
功能性线粒体DNA (mtDNA) 对黑色素瘤生长和转移至关重要. 致病性mtDNA变异阻碍了瘤细胞的循环,这表明mtDNA.
科学领域:
- 癌症生物学 癌症生物学
- 线粒体生物学 线粒体生物学
- 转移研究研究 转移研究
背景情况:
- 线粒体DNA (mtDNA) 突变在癌症中很常见,但它们在瘤进展中的作用仍然存在争议.
- 了解mtDNA对癌症生长和扩散的影响对于开发新疗法至关重要.
研究的目的:
- 研究线粒体DNA (mtDNA) 变异对黑色素瘤瘤生长和转移潜力的影响.
- 阐明mtDNA功能障碍影响癌细胞扩散的机制.
主要方法:
- 创建具有野生型或病原性mtDNA变异的人类黑色素瘤细胞质混合 (cybrid) 细胞系.
- 评估瘤生长,自发转移,以及循环中的瘤细胞数量.
- 对黑色素瘤细胞迁移,入侵,阿诺基斯和器官殖民的分析.
- 评估在异性质细胞系中对mtDNA等位基频率的选择性压力.
主要成果:
- 尽管氧化酸化受损,但同质细胞致病的mtDNA混合体形成了瘤.
- 致病性mtDNA变异显著减少了自发转移和循环黑色素瘤细胞.
- 黑色素瘤细胞迁移和入侵被致病性mtDNA减少,确定循环进入是瓶.
- 在瘤生长过程中,选择性压力抑制了致病性mtDNA等位基因频率.
结论:
- 功能性mtDNA对于使转移进入循环中至关重要.
- mtDNA完整性在黑色素瘤进展和转移潜力中发挥着重要作用.
相关概念视频
Animal Mitochondrial Genetics
7.6K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.6K
Mismatch Repair
4.9K
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...
4.9K
Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
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
Mitochondrial Membranes
11.4K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
11.4K
Cancers Originate from Somatic Mutations in a Single Cell
12.0K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
12.0K


