铁- ((Fe3+) -依赖端粒酶的重新激活驱动结肠直肠癌
Raghuvaran Shanmugam1, Prativa Majee1, Wei Shi1
1Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
Cancer discovery
|June 17, 2024
概括
铁过载和遗传因素通过皮林传感器在结直肠癌中重新激活端粒酶. 一种新型分子SP2509抑制了这一过程,为癌症提供了一个新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 来自饮食或遗传的铁过载与结直肠癌风险有关.
- 金属诱导瘤发生的机制,特别是端粒酶的活性化,尚不清楚.
研究的目的:
- 阐明将铁过载与结直肠癌发生联系起来的分子机制.
- 确定结直肠癌治疗的新型治疗点.
主要方法:
- 对新鲜结直肠癌样本的分析,以确定关键蛋白质.
- 化学遗传选,异热剂量反应指纹和质谱学.
- 研究了人类端粒酶逆转录酶 (hTERT) 的依赖铁的活性化.
主要成果:
- 鉴定Pirin作为一个铁传感器,以铁 (Fe3+) 依赖的方式重新激活端粒酶 (hTERT),驱动结直肠癌.
- 发现了一种小分子SP2509,它通过与铁结合竞争来抑制皮林介导的hTERT反应.
- 建立了铁过载和结直肠癌发病率之间的分子联系.
结论:
- 铁 (Fe3+) 和遗传因素合作重新激活端粒酶,提供与铁有关的结肠直肠癌的机制.
- SP2509是一种新的治疗策略,针对结直肠癌和潜在的其他癌症中的端粒酶再激活.
相关概念视频
Replicative Cell Senescence
3.6K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
Telomeres and Telomerase
23.3K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
23.3K
Adaptive Mechanisms in Cancer Cells
5.7K
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,...
5.7K
Cancer-Critical Genes I: Proto-oncogenes
8.8K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.8K
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
Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.4K


