CDK8是一种结直肠癌瘤基因,它调节β-catenin活性
Ron Firestein1, Adam J Bass, So Young Kim
1Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
Nature
|September 17, 2008
概括
准CDK8,一种在结肠癌中过度表达的基因,抑制癌细胞的增殖. 这一发现表明CDK8是WNT/β-catenin驱动的结肠直肠恶性瘤的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 异常的WNT/β-catenin通路激活是几乎所有结直肠癌的标志.
- 虽然β-catenin驱动结肠瘤发生,但需要额外的遗传变化才能完全恶性转变.
研究的目的:
- 识别调节β-catenin活动的基因,对结肠癌细胞增殖至关重要.
- 研究CDK8在结直肠癌进展中的作用.
主要方法:
- 在人类结肠癌细胞中进行了两次功能丧失查.
- 将选鉴定基因与来自结肠癌样本的副本数量改变数据进行了比较.
- 评估了CDK8抑制对结肠癌细胞增殖和β-catenin标的影响.
主要成果:
- 编码介质复合体成员的CDK8位于13q12.13,在结肠癌中复杂复制数增加的区域.
- 抑制CDK8可以抑制高CDK8和β-catenin活性结肠癌细胞的增殖.
- CDK8激酶活性对于β-catenin驱动的转化和基因表达至关重要.
结论:
- CDK8在结肠癌细胞增殖和恶性转变中发挥着重要作用.
- 对CDK8的治疗向可能为具有WNT/β-catenin通路激活的结直肠癌提供临床益处.
相关概念视频
Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.

