瘤性KRAS重新连接压力颗粒动力学:机制和治疗机会
Msimisi Ndzinisa1, Birhanetensay Masresha Altaye2, Yuh-Pyng Sher3,4,5
1Graduate Institute of Biological Science and Technology, China Medical University, Taichung, Taiwan.
The Kaohsiung journal of medical sciences
|March 2, 2026
概括
癌细胞利用压力颗粒 (SG) 进行生存和治疗抵抗. 针对这些动态结构提供了一个有希望的策略,以提高癌症治疗效率和改善患者的治疗结果.
科学领域:
- 细胞生物学 细胞生物学
- 癌症生物学 癌症生物学
- 生物化学 生物化学
背景情况:
- 压力颗粒 (SGs) 是动态的,在细胞压力下形成的无膜蛋白-RNA凝聚物.
- 癌细胞劫持SG以促进生存,治疗耐药性和瘤攻击性.
- SG形成涉及蛋白质-RNA相互作用,相分离和翻译后修改.
研究的目的:
- 审查压力颗粒在癌细胞存活率和治疗耐药性的作用.
- 要突出癌细胞如何利用SG来适应和持续压力.
- 讨论针对KRAS驱动的癌症中SG的新兴治疗策略.
主要方法:
- 在癌症中压力颗粒动态的文献综述.
- 瘤细胞利用SG进行生存和适应的分析.
- 检查针对SG形成和功能的治疗策略.
主要成果:
- 癌细胞保持SG以缓冲压力并稳定促进生存的转录.
- SGs隔离了益瘤因子并稳定了mRNA,有助于瘤的攻击性.
- 由KRAS驱动的癌症由于瘤信号而表现出增强的SG形成和稳定性.
结论:
- 破坏SG组合或功能可以使瘤对治疗敏感.
- 准SG是一种有前途的治疗方法,用于持续细胞应激的癌症.
- 干扰SG动态可能会改善治疗效率和KRAS驱动癌症患者的治疗结果.
相关概念视频
Small GTPases - Ras and Rho
5.6K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
5.6K
Cancer-Critical Genes I: Proto-oncogenes
11.6K
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...
11.6K
The Ras Gene
7.4K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
7.4K
MAPK Signaling Cascades
8.9K
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...
8.9K
mTOR Signaling and Cancer Progression
5.0K
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...
5.0K
Abnormal Proliferation
5.3K
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...
5.3K


