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

被引：32

作者：

Han, Shiwei ^{[1
,2
,3
,4
]}

Ma, Xuemei ^{[1
,3
,4
]}

Zhao, Yanxia ^{[5
]}

Zhao, Hongying ^{[6
]}

Batista, Ana ^{[2
]}

Zhou, Sheng ^{[7
]}

Zhou, Xiaona ^{[1
,3
,4
]}

Yang, Yao ^{[1
,3
,4
]}

Wang, Tingting ^{[1
,3
,4
]}

Bi, Jingtao ^{[8
]}

Xia, Zheng ^{[9
]}

Bai, Zhigang ^{[1
,3
,4
]}

Garkavtsev, Igor ^{[2
]}

Zhang, Zhongtao ^{[1
,3
,4
]}

机构：

[1] Capital Med Univ, Beijing Friendship Hosp, Dept Gen Surg, Beijing, Peoples R China

[2] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA

[3] Beijing Key Lab Canc Invas & Metastasis Res, Beijing, Peoples R China

[4] Natl Clin Res Ctr Digest Dis, Beijing, Peoples R China

[5] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Ctr Canc, Wuhan, Peoples R China

[6] Capital Med Univ, Beijing Chaoyang Hosp, Dept Pathol, Beijing, Peoples R China

[7] Huazhong Univ Sci & Technol, Inst Pathol, Union Hosp, Tongji Med Coll, Wuhan, Peoples R China

[8] Peking Univ, Dept Gen Surg, Beijing Jishuitan Hosp, Med Coll 4, Beijing, Peoples R China

[9] Cent S Univ, Dept Surg, Xiangya Hosp, Changsha, Hunan, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 28期

基金：

中国国家自然科学基金;

关键词：

gastric cancer; Glypican-3; metastasis; FoxM1; Erk1/2; GOLABI-BEHMEL-SYNDROME; FOXM1; OVERGROWTH; EXPRESSION; PATHWAYS; THERAPY; KINASE; TARGET; TUMORS; CELLS;

D O I：

10.18632/oncotarget.9763

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：44406 / 44416

页数：11

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