Janik Marcelina E, Lityńska Anna, Vereecken Pierre
Department of Glycoconjugate Biochemistry, Institute of Zoology, Jagiellonian University, Krakow, Poland.
Biochim Biophys Acta. 2010 Jun;1800(6):545-55. doi: 10.1016/j.bbagen.2010.03.013. Epub 2010 Mar 20.
Cell migration is an essential process in organ homeostasis, in inflammation, and also in metastasis, the main cause of death from cancer. The extracellular matrix (ECM) serves as the molecular scaffold for cell adhesion and migration; in the first phase of migration, adhesion of cells to the ECM is critical. Engagement of integrin receptors with ECM ligands gives rise to the formation of complex multiprotein structures which link the ECM to the cytoplasmic actin skeleton. Both ECM proteins and the adhesion receptors are glycoproteins, and it is well accepted that N-glycans modulate their conformation and activity, thereby affecting cell-ECM interactions. Likely targets for glycosylation are the integrins, whose ability to form functional dimers depends upon the presence of N-linked oligosaccharides. Cell migratory behavior may depend on the level of expression of adhesion proteins, and their N-glycosylation that affect receptor-ligand binding.
The mechanism underlying the effect of integrin glycosylation on migration is still unknown, but results gained from integrins with artificial or mutated N-glycosylation sites provide evidence that integrin function can be regulated by changes in glycosylation.
A better understanding of the molecular mechanism of cell migration processes could lead to novel diagnostic and therapeutic approaches and applications. For this, the proteins and oligosaccharides involved in these events need to be characterized.
细胞迁移是器官稳态、炎症以及转移（癌症致死的主要原因）过程中的一个重要过程。细胞外基质（ECM）作为细胞黏附和迁移的分子支架；在迁移的第一阶段，细胞与ECM的黏附至关重要。整合素受体与ECM配体的结合导致形成复杂的多蛋白结构，该结构将ECM与细胞质肌动蛋白骨架相连。ECM蛋白和黏附受体均为糖蛋白，并且人们普遍认为N-聚糖可调节它们的构象和活性，从而影响细胞与ECM的相互作用。糖基化的可能靶点是整合素，其形成功能性二聚体的能力取决于N-连接寡糖的存在。细胞迁移行为可能取决于黏附蛋白的表达水平及其影响受体-配体结合的N-糖基化。
整合素糖基化对迁移影响的潜在机制尚不清楚，但从具有人工或突变N-糖基化位点的整合素获得的结果提供了证据，表明整合素功能可通过糖基化变化来调节。
更好地理解细胞迁移过程的分子机制可能会带来新的诊断和治疗方法及应用。为此，需要对参与这些事件的蛋白质和寡糖进行表征。
