干扰ERC1-LL5β相互作用会破坏血相关平台,并影响瘤细胞运动性
Lucrezia Maria Ribolla1, Kristyna Sala1, Diletta Tonoli1
1Vita-Salute San Raffaele University and San Raffaele Scientific Institute, Milano, Italy.
PloS one
|July 12, 2023
概括
破坏LL5β和ERC1蛋白之间的相互作用会抑制瘤细胞的迁移和入侵. 确定了阻断这种相互作用的特定蛋白质碎片,减少了细胞运动性和侵入的形成.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞迁移对于瘤的进展至关重要,并且涉及细胞前端的复杂分子事件.
- 脚手架蛋白LL5β和ERC1被招募到移徙瘤细胞中的血膜平台上,支持突起.
- 减少LL5β或ERC1会损害瘤细胞的运动性和侵入性.
研究的目的:
- 调查干扰LL5β-ERC1相互作用是否可以抑制瘤细胞迁移.
- 为了确定负责LL5β-ERC1相互作用的特定蛋白质碎片.
- 评估破坏这种相互作用的治疗潜力.
主要方法:
- 生物化学表征以识别最小的相互作用碎片 (ERC1 ((270-370) 和LL5β ((381-510)).
- 核磁共振光谱检测证实碎片的乱和相互作用.
- 同免疫沉试验用于评估细胞中的复杂形成和碎片干扰.
- 基于细胞的测试,以评估对细胞移动性,侵入性和入侵性的影响.
主要成果:
- 确定了最小相互作用碎片ERC1 ((270-370) 和LL5β ((381-510),显示出可逆的高亲和度相互作用.
- LL5β(381-510) 片段抑制了细胞中LL5β-ERC1复合物的形成.
- LL5β的表达 ((381-510) 从细胞边缘移除了局部化的内源ERC1并降低了瘤细胞的运动性,入侵的密度和入侵.
结论:
- 破坏LL5β和ERC1之间的异型相互作用有效抑制瘤细胞迁移和入侵.
- 针对这种相互作用的特定蛋白质片段为抗癌疗法提供了潜在的战略.
- 干扰等离子体膜平台上的蛋白质-蛋白质相互作用是抑制癌细胞入侵的可行方法.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
Cancer Cell Migration through Invadopodia
2.3K
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,...
2.3K
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Cell Motility through Blebbing
2.0K
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Blebbing Through the Matrix
In multicellular...
2.0K
Interactions Between Signaling Pathways
6.3K
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...
6.3K


