通过阻断EVH1-WAVE2相互作用,Ena/VASP-EVH1抑制可以防止化疗和转移
Matthias Müller1,2, Matthias Barone2,3, Maarten van Dinther4
1PROSION Therapeutics, Köln 50931, Germany.
概括
针对癌细胞中的Ena/VASP-WAVE2相互作用可以抑制转移. 这一发现为开发抑制癌细胞迁移和改善患者存活率的药物提供了新的策略.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 癌症转移,癌细胞的扩散,是癌症相关死亡的主要原因.
- 癌细胞的运动力,由lamellipodia中的actin动力学驱动,对于转移至关重要.
- 埃纳/VASP蛋白和WAVE调控复合体是actin聚合和细胞迁移的关键调节者.
研究的目的:
- 为了研究Ena/VASP蛋白与癌细胞扩散中的WAVE2之间的交叉对话.
- 评估针对Ena/VASP-WAVE2相互作用抑制癌症转移的治疗潜力.
主要方法:
- 利用WAVE2的基因操纵,包括突变EVH1域识别动机.
- 通过使用三阴性MDA-MB-231乳腺癌细胞评估癌细胞化学反应和扩散.
- 在体内转移和扩散研究中使用斑马鱼和小鼠模型.
- 在临床前转移模型中使用Ena/VASP-EVH1抑制剂.
主要成果:
- 在斑马鱼中,WAVE2基因突变取消了化学反应,并减少了MDA-MB-231细胞的扩散.
- 在小鼠中对突变细胞进行正位素植入,可减少巨变转移并延长存活时间.
- 抑制Ena/VASP-EVH1相互作用显著降低了体内转移.
- 在癌细胞转移中,Ena/VASP-WAVE2相互作用发挥了关键作用.
结论:
- 埃纳/VASP-WAVE2相互作用对于癌细胞迁移和扩散是必不可少的.
- 对这种相互作用的药理定位是减少癌症转移的有希望的治疗策略.
- 干扰Ena/VASP-WAVE2可能提供一种新的方法来提高癌症治疗结果.
相关概念视频
Cancer Cell Migration through Invadopodia
2.4K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.4K
Regulation of Angiogenesis and Blood Supply
2.7K
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...
2.7K
Chemotaxis and Direction of Cell Migration
3.5K
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
3.5K
Mechanism of Angiogenesis
5.8K
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.8K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.3K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.3K
Overview of Cell-Matrix Interactions
7.5K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
7.5K


