Identification of Glypican-3 as a potential metastasis suppressor gene in gastric cancer
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Shiwei Han1,2,3,*, Xuemei Ma1,3,*, Yanxia Zhao4,*, Hongying Zhao5, Ana Batista2, Sheng Zhou6, Xiaona Zhou1,3, Yao Yang1,3, Tingting Wang1,3, Jingtao Bi7, Zheng Xia8, Zhigang Bai1,3, Igor Garkavtsev2, Zhongtao Zhang1,3
1Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
2Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
3Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing, China
4Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
5Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
6Institute of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
7Department of General Surgery, Beijing Jishuitan Hospital, The Fourth Medical College of Peking University, Beijing, China
8Department of Surgery, Xiangya Hospital, Central South University, Changsha, China
*These authors have contributed equally to this work
Shiwei Han, email: firstname.lastname@example.org
Zhongtao Zhang, email: email@example.com
Keywords: gastric cancer, Glypican-3, metastasis, FoxM1, Erk1/2
Received: July 02, 2015 Accepted: May 23, 2016 Published: June 01, 2016
Gastric cancer is a prevalent tumor that is usually detected at an advanced metastatic stage. Currently, standard therapies are mostly ineffective. Here, we report that Glypican-3 (GPC3) is absent in invasive tumors and metastatic lymph nodes, in particular in aggressive and highly disseminated signet ring cell carcinomas. We demonstrate that loss of GPC3 correlates with poor overall survival in patients. Moreover, we show that absence of GPC3 causes up-regulation of MAPK/FoxM1 signaling and that blockade of this pathway alters cellular invasion. An inverse correlation between GPC3 and FoxM1 is also shown in patient samples. These data identify GPC3 as a potential metastasis suppressor gene and suggest its value as a prognostic marker in gastric cancer. Development of therapies targeting signaling downstream of GPC3 are warranted.
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