KRAS和YAP1汇聚在一起,调节EMT和瘤存活率
Diane D Shao1, Wen Xue2, Elsa B Krall1
1Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Cell
|June 24, 2014
概括
瘤性RAS癌细胞的生存取决于突变的RAS. 研究人员发现,YAP1可以替代RAS,调节上皮层-介质细胞过渡 (EMT) 并影响癌症进展.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 遗传学 是一个遗传学.
背景情况:
- 瘤性RAS突变驱动癌细胞存活,但这种依赖的机制尚未完全理解.
- 识别能够补偿RAS功能的基因对于了解癌细胞脆弱性至关重要.
研究的目的:
- 识别能够在癌细胞中功能性取代瘤性RAS的基因.
- 阐明RAS基因依赖的基础分子机制.
主要方法:
- 在一个依赖KRAS的结肠癌细胞系中,系统地表达了15294个开放的读取,具有可诱导的KRAS抑制.
- 对细胞存活和转化在KRAS抑制后的基因功能的分析.
- 在Kras驱动的小鼠肺癌模型中对YAP1信号的研究.
主要成果:
- 确定了147个基因,在KRAS被抑制时促进生存.
- 转录协活性剂YAP1挽救了细胞活力,对KRAS诱导的转化至关重要.
- 在肺癌模型中观察到对KRAS抑制的获得性抵抗中,YAP1信号的增加.
- 发现KRAS和YAP1汇聚在转录因子FOS上,激活了上皮层-介质细胞转换 (EMT) 程序.
结论:
- 由YAP1对EMT的转录调节是瘤性RAS信号的关键组成部分.
- 在依赖RAS的癌症中,YAP1是潜在的治疗标.
相关概念视频
Interactions Between Signaling Pathways
4.7K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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...
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...
4.7K
mTOR Signaling and Cancer Progression
3.6K
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...
3.6K
mTOR Signaling and Cancer Progression
1.5K
1.5K
Abnormal Proliferation
4.0K
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...
4.0K
PI3K/mTOR/AKT Signaling Pathway
5.1K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.1K
Cadherins in Tissue Organization
3.5K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.5K


