细胞动力学失败触发了河马瘤抑制器通路的激活
Neil J Ganem1, Hauke Cornils1, Shang-Yi Chiu1
1Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
在瘤中常见的四体细胞,由于细胞动力学失败和额外的中心体,激活Hippo路径. 这条涉及LATS2的途径稳定p53并抑制YAP/TAZ,作为瘤抑制机制.
科学领域:
- 细胞生物学 细胞生物学
- 癌症生物学 癌症生物学
- 遗传学 是一个遗传学.
背景情况:
- 基因组翻倍的特征是四体性,在大约37%的人类瘤中观察到,可以促进瘤发生.
- 一个依赖p53的屏障通常会抑制四体细胞的增殖,但潜在的细胞缺陷和信号通路仍然基本未知.
研究的目的:
- 为了识别细胞缺陷和信号通路,触发四体细胞的生长抑制.
- 阐明Hippo通路在四平状细胞生长抑制和瘤抑制中的作用.
主要方法:
- 利用RNA干扰 (RNAi) 查来识别涉及到四体细胞生长抑制的基因.
- 采用体外进化方法来研究四体细胞中的适应机制.
- 研究了Hippo通路在培养细胞和自然存在的四体细胞中的激活.
主要成果:
- 证明四类细胞中细胞动能失败会激活Hippo瘤抑制器通路.
- 通过改变小G蛋白信号传递和激活LATS2激酶,表明额外的中心体有助于Hippo通路的诱导.
- 证实LATS2稳定了p53并抑制了YAP和TAZ转录调节器.
结论:
- 河马通路作为关键的瘤抑制机制,由细胞动力学失败和四类细胞中的额外的中心体激活.
- 研究结果揭示了四体细胞是如何被抑制的,并表明瘤细胞潜在的适应机制可以逃避这种调节.
更多相关视频
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
07:26Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
相关概念视频
Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
Hedgehog Signaling Pathway
Abnormal Proliferation
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Cancer-Critical Genes II: Tumor Suppressor Genes
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...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
