Desmocollin‑2 affects the adhesive strength and cytoskeletal arrangement in esophageal squamous cell carcinoma cells.

Desmocollin‑2 affects the adhesive strength and cytoskeletal arrangement in esophageal squamous cell carcinoma cells.
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DOI:
10.3892/mmr.2014.2485
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发表时间:
2014-11
影响因子:
3.4
通讯作者:
Li EM
Li EM
中科院分区:
医学4区
文献类型:
--
作者:
Fang WK;Liao LD;Zeng FM;Zhang PX;Wu JY;Shen J;Xu LY;Li EM

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desmocolin -2 (DSC2)是一种跨膜糖蛋白,属于桥粒钙粘蛋白家族,已被发现在几种类型的癌症中存在差异表达,并参与肿瘤的进展。DSC2在食管鳞状细胞癌(ESCC)中抑制肿瘤转移的特性已被描述,但其对ESCC细胞内聚的贡献仍有待阐明。本研究采用RNA干扰(RNAi)技术,在SHEEC和KYSE510细胞中沉默DSC2的表达。采用悬挂滴法和碎片法研究DSC2在细胞-细胞粘附中的作用。采用Western blot和共聚焦显微镜分析细胞粘附分子的表达和定位以及细胞骨架的排列。结果表明,RNAi敲低DSC2导致细胞-细胞粘附缺陷,并伴随桥粒蛋白表达和粘附连接分子分布的减少。DSC2表达的降低引起游离γ-连环蛋白水平的增加,从而促进其向粘附连接复合体的募集。此外,rnai介导的DSC2抑制导致角蛋白中间丝缩回和丝-肌动蛋白细胞骨架重排。综上所述,这些数据支持了我们之前的发现,并提出DSC2可能通过控制细胞-细胞附着和细胞骨架重排的机制参与细胞侵袭行为的调节。
Desmocollin-2 (DSC2), a transmembrane glycoprotein belonging to the desmosomal cadherin family, has been found to be differentially expressed in several types of cancer and to be involved in tumor progression. The tumor metastasis suppressing property of DSC2 in esophageal squamous cell carcinoma (ESCC) has been described, however, its contribution to cell cohesion in ESCC remains to be elucidated. In the present study, using RNA interference (RNAi), the expression of DSC2 was silenced in SHEEC and KYSE510 cells. Hanging drop and fragmentation assays were performed to investigate the role of DSC2 in cell-cell adhesion. Western blot analysis and confocal microscopy were used to analyze the expression and localization of cell adhesion molecules and cytoskeletal arrangement. The results demonstrated that DSC2 knock down by RNAi caused defects in cell-cell adhesion and a concomitant reduction in desmosomal protein expression and adherens junction molecule distribution. A decrease in the expression of DSC2 caused an increase in free γ-catenin levels, thus promoting its recruitment to the adherens junction complex. In addition, the RNAi-mediated inhibition of DSC2 led to keratin intermediate filament retraction and filamentous-actin cytoskeleton rearrangement. Taken together, these data support our previous findings and the proposal that DSC2 may be involved in the regulation of the invasive behavior of cells by a mechanism that controls cell-cell attachment and cytoskeleton rearrangement.
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