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Abstract |
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| Vol 46 No. 8: 682-690 |
[PDF] [Full Text] |
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| Silencing RhoA inhibits migration and invasion through Wnt/β-catenin pathway and growth through cell cycle regulation in human tongue cancer |
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| Guoxin Yan1,†,
Ronghai Zou1,
Zhenggang Chen2,3,†,
Bing Fan1,
Zhaoyan Wang4,
Ying Wang5,
Xiaonan Yin3,
Dong Zhang6,7,
Lei Tong3,
Fang Yang3,
Weina Jiang8,
Wensheng Fu9,
Jiwei Zheng10,11,†,
Martin O. Bergo12,
Martin Dalin12,
Jiawei Zheng2,*,
Shulan Chen3 and
Jianhua Zhou3
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1Department of Stomatology, Wuxi No.2 People's Hospital, Wuxi 214002, China
2Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
3Department of Stomatology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China
4Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China
5Department of Pediatrics, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China
6Department of Oral Maxillofacial Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
7Department of Cancer, Stomatology Research Center, Shandong University, Jinan 250012, China
8Department of Pathology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China
9Department of Oncology, Qingdao Hiser Medical Group, Qingdao 266033, China
10School of Stomatology, Xuzhou Medical College, Jiangsu 221004, China
11Department of Stomatology, Affiliated Hospital of Xuzhou Medical College, Jiangsu 221004, China
12Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Cancer Center, Gothenburg University, Gothenburg S-413 90, Sweden
† These authors contributed equally to this work.
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Abstract Ras homolog gene family member A (RhoA) has been identified as a critical regulator of tumor aggressive behavior. In this study, we assessed the role of RhoA in the mechanisms underlying growth, migration, and invasion of squamous cell carcinoma of tongue (TSCC). Stable RhoA knockdown of TSCC cell lines SCC-4 and CAL27 were achieved using Lentiviral transfection. The effects of RhoA depletion on cell migration, invasion, and cell proliferation were determined. The possible underlying mechanism of RhoA depletion on TSCC cell line was also evaluated by determining the expression of Galectin-3 (Gal-3), β-catenin, and matrix metalloproteinase-9 (MMP-9) in vivo. Meanwhile, the underlying mechanism of TSCC growth was studied by analysis of cyclin D1/2, p21CIP1/WAF1, and p27Kip1 protein levels. Immunohistochemical assessments were performed to further prove the alteration of Gal-3 and β-catenin expression. We found that, in mice injected with human TSCC cells in the tongue, RhoA levels were higher in primary tumors and metastasized lymph nodes compared with those in the normal tissues. Silencing of RhoA significantly reduced the tumor growth, decreased the levels of Gal-3, β-catenin, MMP-9, and cyclin D1/2, and increased the levels of p21CIP1/WAF1 and p27Kip1. In vitro, RhoA knockdown also led to inhibition of cell migration, invasion, and proliferation. Our data suggest that RhoA plays a significant role in TSCC progression by regulating cell migration and invasion through Wnt/β-catenin signaling pathway and cell proliferation through cell cycle regulation, respectively. RhoA might be a novel therapeutic target of TSCC. |
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Keywords RhoA; tumor invasion; metastasis; tumor growth; Wnt/β-catenin signaling pathway |
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Received 2014-1-6
Accepted 2014-4-18 |
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Funding This work was supported by the grants from the National Natural Science Foundation of China (81372908), Doctoral Science Grant of China (2013M541530), Qingdao Municipal Science & Technology Commission (2012-1-3-1-(16)-nsh), and Jiangsu College Natural Sci |
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* Correspondence address Tel: +86-21-23271063; Fax: +86-21-63121780; E-mail: [email protected] |
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