文章基本信息

标题：Site-specific N-glycosylation of integrin α2 mediates collagen-dependent cell survival
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作者：Yen-Lin Huang ; Ching-Yeu Liang ; Vera Labitzky 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：10
页码：1-27
DOI：10.1016/j.isci.2021.103168
语种：English
出版社：Elsevier
摘要：SummaryIntegrin alpha 2 (ITGA2) promotes cancer metastasis through selective adhesion to ECM proteins; however, the specific contribution of integrin glycosylation remains uncertain. We provide evidence that ITGA2 is a highly glycosylated transmembrane protein expressed in ovarian cancer tissue and cell lines. In-depth glycoproteomics identified predominantN- andO-glycosylation sites harboring substantially divergent ITGA2 glycosylation profiles. Generated putative ITGA2N-glycosite mutants halted collagen and laminin binding and cells lackingN-glycosylated ITGA2 were marginally adherent to collagen, likely associated with its enhanced proteasome degradation through poly-ubiquitination. Proteomic and enrichment pathway analysis revealed increased cellular apoptosis and collagen organization in non-glycosylated ITGA2 mutant cells. Moreover, we provide evidence that ITGA2-specific sialylation is involved in selective cell-ECM binding. These results highlight the importance of glycans in regulating ITGA2 stability and ligand binding capacity which in turn modulates downstream focal adhesion and promotes cell survival in a collagen environment.Graphical abstractDisplay OmittedHighlights•In-depth glycoproteomics reveal divergent ITGA2 glycosylation•Site-specific N-glycans regulate protein stability and ECM ligand binding affinity•Loss of N-glycosylation induces proteasome degradation through poly-ubiquitination•N-glycosylation mediates collagen-dependent cell survival through focal adhesionCell biology; Proteomics; Cancer