通过激活GCN2/eIF2α/ATF4信号传导,ETHE1可以加速三阴性乳腺癌转移
Shao-Ying Yang1,2,3, Li Liao1,2,3, Shu-Yuan Hu1
1Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
通过增强eIF2α酸化和ATF4表达,ETHE1促进三阴性乳腺癌 (TNBC) 转移. 用ISRIB向ETHE1或eIF2α酸化为TNBC提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症转移研究 癌症转移研究
背景情况:
- 三阴性乳腺癌 (TNBC) 是一种具有有限治疗选择的侵袭性亚型.
- 了解TNBC转移机制对于开发有效疗法至关重要.
- 目前尚不清楚ETHE1与乙基马龙性脑病相关的TNBC中的作用.
研究的目的:
- 研究ETHE1在三阴性乳腺癌进展中的功能和机制.
- 为了确定TNBC转移的潜在治疗点.
主要方法:
- 产生具有ETHE1过度表达或淘汰的稳定细胞系.
- 细胞迁移和侵入的体外测定.
- 在小鼠模型中的肺转移体内研究.
- 质谱仪用于分子机制分析.
- 西方涂抹和共同免疫沉以研究蛋白质相互作用.
主要成果:
- 在体内,ETHE1过度表达显著促进了TNBC细胞迁移,入侵和肺转移,但没有影响扩散或瘤生长.
- ETHE1的转移前作用独立于其酶活性.
- 通过促进eIF2α-GCN2相互作用,ETHE1增强了eIF2α酸化,导致ATF4表达的增加.
- 抑制eIF2α酸化或ATF4倒置部分逆转ETHE1的转移前效应.
结论:
- 在通过eIF2α/ATF4通路促进TNBC转移方面,ETHE1起着至关重要的作用.
- ETHE1代表了攻击性TNBC的潜在治疗标.
- 作为eIF2α酸化的抑制剂,ISRIB在治疗ETHE1驱动的TNBC转移方面表现有前途.
更多相关视频
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
10:32Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs
Published on: December 19, 2019
相关概念视频
Mitogens and the Cell Cycle
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
PI3K/mTOR/AKT Signaling Pathway
Cancer-Critical Genes I: Proto-oncogenes
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...
