在肺腺癌中,UHRF1是KRAS驱动性瘤发生的调解者
Kaja Kostyrko1, Marta Román2, Alex G Lee2
1Division of Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA. kaja.kostyrko@ucsf.edu.
Nature communications
|July 5, 2023
概括
研究人员确定含有PHD和RING指域1 (UHRF1) 的Ubiquitin-like作为KRAS突变肺癌的漏洞. 针对UHRF1可能为这些特定的肺癌患者提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 克拉斯突变是肺癌的常见驱动因素,需要针对性治疗.
- 识别KRAS特定的漏洞对于开发有效的肺癌治疗非常重要.
研究的目的:
- 为了发现肺癌中KRAS特定的漏洞.
- 研究表观遗传调节器UHRF1在KRAS驱动的肺癌中的作用.
主要方法:
- 在原发性小鼠肺癌中的RNAi屏幕球体.
- 在人类肺癌模型中UHRF1淘汰.
- 全基因组甲基化和基因表达分析.
- 通过CRISPR/Cas9查和体内瘤生长研究.
主要成果:
- 在KRAS突变肺癌细胞中,UHRF1淘汰会选择性地抑制生长,并诱导细胞亡.
- UHRF1的枯竭导致了全球DNA低甲基化和瘤抑制基因 (TSG) 的上调.
- 在体内,UHRF1淘汰在KRAS驱动的肺癌模型中抑制了瘤生长.
- 患者的高UHRF1表达与TSG表达下降和KRAS突变肺癌的较差结果相关.
结论:
- 在肺癌中,UHRF1 是一种KRAS 特定的漏洞.
- UHRF1代表了KRAS突变肺癌的潜在治疗标.
相关概念视频
The Ras Gene
6.3K
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...
Ras is a...
6.3K
Small GTPases - Ras and Rho
4.0K
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:
4.0K
Mitogens and the Cell Cycle
6.6K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
MAPK Signaling Cascades
5.7K
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...
5.7K
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
mTOR Signaling and Cancer Progression
3.8K
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...
3.8K


