Chi-Hau Chen1, Ming-Kwang Shyu2, Shu-Wei Wang3, Chih-Hsing Chou3, Miao-Juei Huang3, Tzu-Chi Lin3, Syue-Ting Chen3, Ho-Hsiung Lin2, Min-Chuan Huang4. 1. Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan. 2. Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan. 3. Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan. 4. Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: mchuang@ntu.edu.tw.
Abstract
OBJECTIVE: Mucin (MUC) 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 β1 and phosphorylation of focal adhesion kinase (FAK). The enhancement of cell motility and the integrin β1 signaling by MUC20 was significantly suppressed by integrin β1 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 β1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis.
OBJECTIVE:Mucin (MUC) 20 has recently been implicated to play a role in humancarcinogenesis. 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 β1 and phosphorylation of focal adhesion kinase (FAK). The enhancement of cell motility and the integrin β1 signaling by MUC20 was significantly suppressed by integrin β1 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 β1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis.
Authors: Ayse L Mindikoglu; Mustafa M Abdulsada; Antrix Jain; Jong Min Choi; Prasun K Jalal; Sridevi Devaraj; Melissa P Mezzari; Joseph F Petrosino; Antone R Opekun; Sung Yun Jung Journal: J Proteomics Date: 2020-01-09 Impact factor: 4.044
Authors: Bo Xue; Wen-Min Guo; Jie-Dong Jia; Gaohaer Kadeerhan; Hua-Ping Liu; Tao Bai; Yuan Shao; Dong-Wen Wang Journal: Am J Cancer Res Date: 2022-02-15 Impact factor: 6.166