Loss of (cid:1) -Dystroglycan Laminin Binding in Epithelium-derived Cancers Is Caused by Silencing of LARGE
Loss of (cid:1) -Dystroglycan Laminin Binding in Epithelium-derived Cancers Is Caused by Silencing of LARGE
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发表时间：
2020
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通讯作者：
Daniel Beltrán-Valero de Bernabé;Kei-ichiro Inamori;T. Yoshida-Moriguchi;C. Weydert;Hollie A. Harper;T. Willer;Michael D. Henry;Kevin P. Campbell
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作者：
Daniel Beltrán-Valero de Bernabé;Kei-ichiro Inamori;T. Yoshida-Moriguchi;C. Weydert;Hollie A. Harper;T. Willer;Michael D. Henry;Kevin P. Campbell
上皮细胞和细胞外基质之间的相互作用对组织结构和功能至关重要，并且在癌症进展过程中受到损害。糖醛酸失调是一种膜受体，介导各种上皮细胞和基底膜之间的相互作用。在许多上皮源性癌症中，表达(cid:2) -三磷酸腺苷异常，但未检测到(cid:1) -三磷酸腺苷异常。在这里，我们报道了(cid:1) -糖质失调聚糖在乳腺癌、宫颈癌和肺癌的高转移上皮细胞系中被正确表达并转运到细胞膜上，但由于类乙酰氨基葡萄糖转移酶（LARGE）基因的沉默而缺乏层粘连蛋白结合。在这些癌细胞中外源性表达LARGE可恢复正常的糖基化和层粘连蛋白结合(cid:1) -三聚糖酐。
The interaction between epithelial cells and the extracellular matrix is crucial for tissue architecture and function and is compromised during cancer progression. Dystroglycan is a membrane receptor that mediates interactions between cells and basement membranes in various epithelia. In many epi-thelium-derived cancers, (cid:2) -dystroglycan is expressed, but (cid:1) -dystroglycan is not detected. Here we report that (cid:1) -dystro-glycan is correctly expressed and trafficked to the cell membrane but lacks laminin binding as a result of the silencing of the like-acetylglucosaminyltransferase ( LARGE ) gene in a cohort of highly metastatic epithelial cell lines derived from breast, cervical, and lung cancers. Exogenous expression of LARGE in these cancer cells restores the normal glycosylation and laminin binding of (cid:1) -dystroglycan,