对瘤性Ras激活在癌症中的网络分析
Edward C Stites1, Paul C Trampont, Zhong Ma
1Beirne B. Carter Center for Immunology Research and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
概括
研究人员模拟了Ras信号,以了解导致癌症的突变. 这揭示了系统级的过程,解释了为什么某些Ras突变在癌症中很常见,并建议针对性的药物策略.
科学领域:
- 分子生物学分子生物学
- 系统生物学 系统生物学
- 癌症研究 癌症研究
背景情况:
- 不调节的Ras信号是许多癌症的标志.
- 激活Ras点突变在瘤发生过程中至关重要,但突变的特定选择仍然不清楚.
- 了解Ras网络动态是开发有效癌症疗法的关键.
研究的目的:
- 开发和验证Ras信号的数学模型,以研究癌症中不受管制的激活.
- 解释Ras点突变在癌症中的差异性患病率.
- 确定针对瘤性Ras网络的新型治疗策略.
主要方法:
- 开发和验证Ras信号通路的数学模型.
- 使用开发的模型对Ras突变物的计算分析.
- 模型预测的实验验证.
- 选择性抑制药物策略的形鉴定.
主要成果:
- 该模型解释了为什么只有具有体外转化潜力的Ras突变子集在癌症中普遍存在.
- 发现了一种系统级的过程,该过程有助于癌细胞中总的Ras激活,并得到实验支持.
- 确定了一种药物策略,优先抑制癌症Ras网络,而不是野生类型网络.
结论:
- 数学建模为癌症中复杂的Ras信号网络提供了关键的见解.
- 这项研究阐明了瘤性Ras突变选择背后的一个关键机制.
- 系统级分析为开发向癌症治疗提供了一个有希望的途径.
相关概念视频
The Ras Gene
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 superfamily...
Ras is a superfamily...
The Ras Gene
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 superfamily...
Ras is a superfamily...
Small GTPases - Ras and Rho
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:
mTOR Signaling and Cancer Progression
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...
mTOR Signaling and Cancer Progression
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...
Cancer-Critical Genes I: Proto-oncogenes
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...

