MUC15 域内结构结构调节整合蛋白聚类以控制癌症转移
Simei Zhang1,2,3, Hongyuan Zhu4,5, Zeen Zhu1,2,6
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|October 13, 2025
概括
细胞表面糖蛋白的尺寸分布,如MUC15,是癌症转移的关键因素. 葡萄糖体结构在物理上控制细胞粘附和转移潜力,提供新的治疗点.
科学领域:
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 癌症转移受到物理线索的影响,如矩阵刚度和带密度.
- 复杂的碳水化合物层,细胞表面的葡萄糖,越来越多地被认为是其在细胞过程中的作用.
研究的目的:
- 识别和描述细胞表面甘油结构作为癌症转移的调节者的作用.
- 调查糖蛋白大小分布如何影响整合素粘附和转移结果.
主要方法:
- 利用数学建模和域截断实验来分析糖蛋白的功能.
- 研究了MUC15 (一种小型糖蛋白) 与焦点粘附和整体素的相互作用.
- 使用胰腺癌模型进行了体内研究,以验证发现.
主要成果:
- 糖蛋白大小分布,以MUC15为例,决定了整合蛋白粘附状态和转移潜力.
- MUC15的抗转移效应取决于其ectodomain,表明一个物理机制.
- 在体内调节MUC15水平改变了转移,与数学预测保持一致.
结论:
- 细胞表面葡萄糖结构是一种癌症进展的新型机械调节器.
- 糖蛋白大小分布是癌症转移的一个关键决定因素.
- 向糖蛋白大小为癌症转移提供了潜在的治疗策略.
相关概念视频
Cadherins in Tissue Organization
3.9K
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...
3.9K
Integrins
5.2K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
5.2K
Cancer Cell Migration through Invadopodia
3.2K
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,...
3.2K
Intracellular Signaling Affects Focal Adhesions
3.5K
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...
3.5K
Activation of Integrins
4.9K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
4.9K
Selectins
4.1K
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
4.1K


