相关实验视频

Updated: Jul 8, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

野生型C-Raf基因剂量和二元化驱动前列腺癌转移

Lisa Ta¹, Brandon L Tsai², Weixian Deng³

¹Department of Molecular and Medical Pharmacology, University of California, Los Angeles; Los Angeles, CA 90095, USA.

|December 13, 2023

概括

野生型C-Raf过度表达通过形成二元体而不是通过激酶活性驱动癌症转移. 针对C-Raf异构体信号提供了转移性疾病的新治疗策略.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
细胞信号传递细胞信号传递

背景情况:

突变的Ras和Raf激酶是通过Ras/Raf/MEK/ERK (MAPK) 途径进行癌症转移的已知驱动因素.
越来越多地认识到非突变 (野生型) Raf 在转移中的作用,但其潜在机制尚未完全理解.
野生型Raf家族成员 (C-Raf,A-Raf或B-Raf) 的高表达可以独立地促进转移性过程.

研究的目的:

研究野生型C-Raf在促进癌症转移中的作用.
阐明野生型C-Raf导致转移的特定机制.
根据C-Raf功能确定治疗转移性疾病的潜在治疗点.

主要方法:

利用体内模型评估野生型C-Raf过度表达对前列腺细胞转移的影响.
进行了转录组和蛋白组分析,以了解信号变化.
使用C-Raf突变物和内源的Raf单体淘汰物来剖析酶活性和二元化的作用.

主要成果:

野生型C-Raf过度表达促进了基因剂量依赖的方式转移.
由C-Raf驱动的转移与上调的MAPK信号相关.
对于促进转移而言,C-Raf的二分化域,而不是其激酶活性,是至关重要的.
C-Raf与其他Raf分子形成异构体的能力对于其前转移性功能至关重要.

结论:

野生类型的C-Raf通过独立于其酶活性的二分化依赖信号促进癌症转移.
C-Raf异构体的形成是驱动转移的一个关键机制.
准野生型C-Raf异构体信号提供了一个有前途的治疗策略,用于管理转移性癌症.

关键词:

生物化学生物化学癌症癌症癌症癌症分子生物学分子生物学蛋白质组学是指蛋白质组学.文字转录学 (Transcriptomics) 是一个学科.

更多相关视频

Author Spotlight: Integrating BRET-Based Assays and Rare Mutation Analysis to Decipher RAF Kinase Regulation in Live Cells

Author Spotlight: Integrating BRET-Based Assays and Rare Mutation Analysis to Decipher RAF Kinase Regulation in Live Cells

Published on: March 1, 2024

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

相关概念视频

The Ras Gene

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...

Small GTPases - Ras and Rho

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:

MAPK Signaling Cascades

MAPK Signaling Cascades

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...

Cancer-Critical Genes I: Proto-oncogenes

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...

Abnormal Proliferation

Abnormal Proliferation

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...

mTOR Signaling and Cancer Progression

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...