Oncotarget

Research Papers:

Identification of Glypican-3 as a potential metastasis suppressor gene in gastric cancer

Shiwei Han _, Xuemei Ma, Yanxia Zhao, Hongying Zhao, Ana Batista, Sheng Zhou, Xiaona Zhou, Yao Yang, Tingting Wang, Jingtao Bi, Zheng Xia, Zhigang Bai, Igor Garkavtsev and Zhongtao Zhang

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Oncotarget. 2016; 7:44406-44416. https://doi.org/10.18632/oncotarget.9763

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Abstract

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

Correspondence to:

Shiwei Han, email: shiwei@steele.mgh.harvard.edu

Zhongtao Zhang, email: zhangzht@medmail.com.cn

Keywords: gastric cancer, Glypican-3, metastasis, FoxM1, Erk1/2

Received: July 02, 2015     Accepted: May 23, 2016     Published: June 01, 2016

ABSTRACT

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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