Regulation of CXCR4/AKT-signaling-induced cell invasion and tumor metastasis by RhoA, Rac-1, and Cdc42 in human esophageal cancer

被引：28

作者：

Guo, Jing ^{[1
]}

Yu, Xiaofang ^{[2
]}

Gu, Jie ^{[3
]}

Lin, Zongwu ^{[3
]}

Zhao, Guangyin ^{[4
]}

Xu, Fengkai ^{[3
]}

Lu, Chunlai ^{[3
]}

Ge, Di ^{[3
]}

机构：

[1] Ningbo 1 Hosp, Dept Thorac Surg, Ningbo, Zhejiang, Peoples R China

[2] Fudan Univ, Dept Nephrol, Zhongshan Hosp, Shanghai 200433, Peoples R China

[3] Fudan Univ, Zhongshan Hosp, Dept Thorac Surg, 180 Fenglin RD, Shanghai 200032, Peoples R China

[4] Shanghai Jiao Tong Univ, Shanghai Hosp 1, Shanghai 200030, Peoples R China

来源：

TUMOR BIOLOGY | 2016年 / 37卷 / 05期

基金：

中国国家自然科学基金;

关键词：

CXCR4; Chemokines; Esophageal neoplasms; Neoplasm metastasis; PI3K/AKT; CHEMOKINE RECEPTOR CXCR4; LYMPH-NODE METASTASIS; SQUAMOUS-CELL; PROGNOSTIC-SIGNIFICANCE; FACTOR-I; EXPRESSION; CARCINOMA; PATTERN; GTPASES; PATHWAY;

D O I：

10.1007/s13277-015-4504-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

CXC chemokines and their cognate receptors have been implicated wildly in cancer pathogenesis. In the present study, we report a critical cause relationship between CXCR4 expression and tumorigenesis in the setting of human esophageal squamous cell carcinoma (ESCC). In ESCC cells, CXCR4 expression was significantly higher than in human esophageal epithelial cells (HEEC). Reduction of CXCR4 in ESCC cells reduced cell proliferation and invasion in vitro and tumor growth in vivo. Among the potential downstream targets of CXCR4-CXCL12 are RhoA, Rac-1, and Cdc42, which are likely to contribute to the invasiveness of ESCC cells. Finally, we found that CXCR4-CXCL12/ AKT axis regulates RhoA, Rac-1, and Cdc42 to modulate cell invasion and tumor metastasis. Together, these results demonstrate a role for CXCR4 in ESCC metastasis and progression and suggest potential targets for therapeutic intervention.

引用

页码：6371 / 6378

页数：8

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