MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin β1 pathway
MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin β1 pathway
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DOI：
10.1016/j.ygyno.2015.11.025
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发表时间：
2016-01-01
影响因子：
4.7
通讯作者：
Huang, Min-Chuan
中科院分区：
文献类型：
--
作者：
Chen, Chi-Hau;Shyu, Ming-Kwang;Huang, Min-Chuan
Objective.粘蛋白（MIX）20最近被认为在人类致癌作用中发挥作用。然而，MUC20在上皮性卵巢癌（EOC）中的作用仍有待阐明。通过免疫组织化学方法评估上皮性卵巢癌患者的组织芯片和肿瘤标本中MUC20的表达。在MUC20过表达或敲低的EOC细胞中分析MUC20对细胞活力、粘附、迁移和侵袭的影响。Western blotting分析MUC20对细胞信号通路的调控。MUC20在卵巢上皮癌组织中的表达高于良性肿瘤组织。MUC20高表达与晚期疾病患者的总体生存率低显著相关。MUC20过表达显著增强EOC细胞的迁移和侵袭，但不增强细胞活力。机制研究表明，MUC20增加细胞与细胞外基质（ECM）蛋白的粘附，并增强整合素β 1的活化和粘着斑激酶（FAK）的磷酸化。MUC20对细胞运动性和整合素β 1信号传导的增强作用被整合素β 1阻断抗体显著抑制。此外，MUC20对EOC细胞的这些作用也在MUC20敲低细胞中得到证实。我们的研究结果表明，MUC20通过激活整合素β 1信号增强EOC细胞的侵袭行为，并为MUC20在卵巢癌转移中的作用提供了新的见解。(c)2015 Elsevier Inc. All rights reserved.
Objective. Mucin (MIX) 20 has recently been implicated to play a role in human carcinogenesis. However, the role of MUC20 in epithelial ovarian cancer (EOC) remains to be elucidated.Methods. MUC20 expression was assessed in tissue microarray and tumor specimens of EOC patients by immunohistochemistry. Effects of MUC20 on cell viability, adhesion, migration, and invasion were analyzed in MUC20 overexpressing or knockdown EOC cells. Western blotting was performed to analyze signaling pathways modulated by MUC20.Results. MUC20 was overexpressed in EOC samples compared with benign tissues. High MUC20 expression was significantly associated with poor overall survival in patients with advanced-stage disease. MUC20 overexpression significantly enhanced EOC cell migration and invasion, but not viability. Mechanistic investigations showed that MUC20 increased cell adhesion to extracellular matrix (ECM) proteins and enhanced activation of integrin beta 1 and phosphorylation of focal adhesion kinase (FAK). The enhancement of cell motility and the integrin beta 1 signaling by MUC20 was significantly suppressed by integrin beta 1 blocking antibody. Furthermore, these effects of MUC20 on EOC cells were also demonstrated in MUC20 knockdown cells.Conclusions. Our results suggest that MUC20 enhances aggressive behaviors of EOC cells by activating integrin beta 1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis. (c) 2015 Elsevier Inc. All rights reserved.