Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets.
Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets.
复制标题
DOI：
10.1017/s1462399409001355
复制
发表时间：
2010-01-18
影响因子：
6.2
通讯作者：
Stipp CS
中科院分区：
文献类型：
--
作者：
Stipp CS
在细胞粘附受体的整联蛋白家族内，整联蛋白α3β1、α6β1、α6β4和α7β1组成层粘连蛋白结合亚家族。文献对这些层粘连蛋白结合整合素在转移中的作用存在分歧，不同的研究表明促转移或抗转移功能。层粘连蛋白结合整合素在不同环境中的相反作用可能部分来自于它们与四跨膜蛋白的异常强大的关联。四跨膜蛋白将整联蛋白组织成称为四跨膜蛋白富集微结构域（TEM）的离散质膜结构域内的多蛋白复合物。TEM协会是至关重要的惊人的快速细胞迁移介导的一些层粘连蛋白结合整合素。然而，新出现的数据表明，层粘连蛋白结合整合素也促进稳定的E-钙粘蛋白为基础的细胞连接，四跨膜蛋白是必不可少的，以及这一功能。因此，TEM关联赋予层粘连蛋白结合整合素促侵袭功能（快速迁移）和抗侵袭功能（稳定的细胞连接），并且TEM在不同细胞类型中的组成可能有助于确定这些相反活性之间的平衡。解开调节层粘连蛋白结合整合素的四跨膜蛋白控制机制将有助于定义抑制这些整合素的功能将是有益的而不是有害的设置，并可能创造机会以比简单的功能阻断更复杂的方式调节整合素活性。
Within the integrin family of cell adhesion receptors, integrins α3β1, α6β1, α6β4 and α7β1 make up a laminin-binding subfamily. The literature is divided on the role of these laminin-binding integrins in metastasis, with different studies indicating either pro- or antimetastatic functions. The opposing roles of the laminin-binding integrins in different settings might derive in part from their unusually robust associations with tetraspanin proteins. Tetraspanins organise integrins into multiprotein complexes within discrete plasma membrane domains termed tetraspanin-enriched microdomains (TEMs). TEM association is crucial to the strikingly rapid cell migration mediated by some of the laminin-binding integrins. However, emerging data suggest that laminin-binding integrins also promote the stability of E-cadherin-based cell–cell junctions, and that tetraspanins are essential for this function as well. Thus, TEM association endows the laminin-binding integrins with both pro-invasive functions (rapid migration) and anti-invasive functions (stable cell junctions), and the composition of TEMs in different cell types might help determine the balance between these opposing activities. Unravelling the tetraspanin control mechanisms that regulate laminin-binding integrins will help to define the settings where inhibiting the function of these integrins would be helpful rather than harmful, and may create opportunities to modulate integrin activity in more sophisticated ways than simple functional blockade.