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首页> 外文OA文献 >Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells.
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Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells.

机译：zonula occludens-2在人肺癌细胞中调节1型膜基质金属蛋白酶表达。

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During tumor invasion, tumor epithelial cells acquire migratory and invasive properties involving important phenotypic alterations. Among these changes, one can observe reorganization or a loss of cell-cell adhesion complexes such as tight junctions (TJs). TJs are composed of transmembrane proteins (occludin, claudins) linked to the actin cytoskeleton through cytoplasmic adaptor molecules including those of the zonula occludens family (ZO-1, -2, -3). We here evaluated the potential role of ZO-2 in the acquisition of invasive properties by tumor cells. In vivo, we showed a decrease of ZO-2 expression in bronchopulmonary cancers, with a preferential localization in the cytoplasm. In addition, in vitro, the localization of ZO-2 varied according to invasive properties of tumor cells, with a cytoplasmic localization correlating with invasion. In addition, we demonstrated that ZO-2 inhibition increases invasive and migrative capacities of invasive tumor cells. This was associated with an increase of MT1-MMP. These results suggest that ZO-2, besides its structural role in tight junction assembly, can act also as a repressor of tumor progression through its ability to reduce the expression of tumor-promoting genes in invasive tumor cells.
机译：在肿瘤侵袭期间，肿瘤上皮细胞具有涉及重要表型改变的迁移和侵袭特性。在这些变化中，可以观察到重组或细胞-细胞粘附复合物（如紧密连接（TJ））的丢失。 TJ由跨膜蛋白（occludin，claudins）组成，该蛋白通过细胞质衔接子分子连接到肌动蛋白的细胞骨架上，包括质子闭合带家族（ZO-1，-2，-3）。我们在这里评估了ZO-2在肿瘤细胞获得侵袭特性中的潜在作用。在体内，我们显示支气管肺癌中ZO-2表达的减少，并优先定位于细胞质中。另外，在体外，ZO-2的定位根据肿瘤细胞的侵袭特性而变化，胞质定位与侵袭相关。此外，我们证明了ZO-2抑制作用可增加侵袭性肿瘤细胞的侵袭和迁移能力。这与MT1-MMP的增加有关。这些结果表明，ZO-2除了在紧密连接装配中的结构作用外，还可以通过其减少侵袭性肿瘤细胞中促肿瘤基因表达的能力来抑制肿瘤的进展。

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