Identification of Glypican-3 as a potential metastasis suppressor gene in gastric cancer.
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.
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing, China.
Shiwei
S
Han
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing, China.
Xuemei
X
Ma
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yanxia
Y
Zhao
Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Hongying
H
Zhao
Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
Ana
A
Batista
Institute of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Sheng
S
Zhou
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing, China.
Xiaona
X
Zhou
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing, China.
Yao
Y
Yang
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing, China.
Tingting
T
Wang
Department of General Surgery, Beijing Jishuitan Hospital, The Fourth Medical College of Peking University, Beijing, China.
Jingtao
J
Bi
Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
Zheng
Z
Xia
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing, China.
Zhigang
Z
Bai
Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
Igor
I
Garkavtsev
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing, China.
Zhongtao
Z
Zhang
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D053673:Glypicans / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans
Erk1/2; FoxM1; Glypican-3; gastric cancer; metastasis