亚致命的细胞染色体c释放产生耐药的持续细胞
Halime Kalkavan1, Mark J Chen1, Jeremy C Crawford1
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cell
|September 2, 2022
概括
药物耐受性持续细胞逃避癌症治疗. 致死性线粒体损伤和细胞染色体c的释放引发了应激反应,形成了易受铁死影响的持续性细胞.
科学领域:
- 细胞生物学
- 癌症研究
- 分子瘤学
背景情况:
- 耐药性持久细胞 (持久细胞) 是癌症治疗中的一个重要障碍,避免治疗诱导的亡.
- 对于开发更有效的癌症疗法至关重要.
研究的目的:
- 研究产生耐药性持续细胞的分子机制.
- 找出关键的信号通路,涉及到细胞存活及其脆弱性.
主要方法:
- 在癌症模型中利用亲细胞缩BH3模拟剂诱导持续细胞形成.
- 研究了线粒体外膜透 (MOMP) 和细胞染色体c释放.
- 分析了综合应激反应 (ISR),血红素调节抑制剂 (HRI) 激酶和ATF4在持续细胞生成中的作用.
主要成果:
- 经过BH3模拟治疗的细胞表现出持续的表型,包括体内殖民和转移.
- 对于产生持久性细胞来说,潜致死的MOMP和全细胞染色体c的释放是必不可少的.
- 持久性细胞的产生独立于细胞和酶的激活,但需要细胞基因组c,HRI激酶,ISR和ATF4.
结论:
- 亚致死性细胞染色体c释放将亚致死性MOMP与酶独立的ATF4激活联系起来,从而建立了耐药的持久性表型.
- 持续性细胞通过GPX4抑制对ferroptosis诱导的敏感性增加.
- 这些发现揭示了持续细胞生成的新途径,并建议针对该机制的潜在治疗策略.
相关概念视频
Treatment Resistant Cancers
3.4K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
Stringent Response in E. coli
43
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
43
Development of Antibiotic Resistance
147
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
147
Desensitization and Tachyphylaxis
2.1K
Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
2.1K
Cytotoxic T Cells-mediated Immune Response
1.2K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
1.2K
Endospores and Sporulation
290
Endospores are specialized, dormant cells primarily formed by Gram-positive bacteria, including Bacillus and Clostridium, enabling survival under extreme environmental conditions. Due to their unique composition and formation process, these structures are highly resistant to physical and chemical insults, such as extreme heat, ultraviolet and ionizing radiation, desiccation, and toxic chemicals. Rare instances of endospore-like structures have also been observed in some Gram-negative bacteria,...
290


