SDF-1/CXCR4 promotes epithelial-mesenchymal transition and progression of colorectal cancer by activation of the Wnt/β-catenin signaling pathway

被引：131

作者：

Hu, Ting-hua ^{[1
]}

Yao, Yu ^{[2
]}

Yu, Shuo ^{[3
]}

Han, Li-li ^{[2
]}

Wang, Wen-juan ^{[2
]}

Guo, Hui ^{[2
]}

Tian, Tao ^{[2
]}

Ruan, Zhi-pin ^{[2
]}

Kang, Xiao-min ^{[2
]}

Wang, Jing ^{[2
]}

Wang, Shu-hong ^{[2
]}

Nan, Ke-jun ^{[2
]}

机构：

[1] Xi An Jiao Tong Univ, Coll Med, Affiliated Hosp 1, Dept Resp, Xian 710061, Shaanxi Provinc, Peoples R China

[2] Xi An Jiao Tong Univ, Coll Med, Affiliated Hosp 1, Dept Oncol, Xian 710061, Shaanxi Provinc, Peoples R China

[3] Xi An Jiao Tong Univ, Coll Med, Affiliated Hosp 2, Dept Gen Surg, Xian 710004, Shaanxi Provinc, Peoples R China

来源：

CANCER LETTERS | 2014年 / 354卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Colorectal cancer; CXCR4; Wnt/beta-catenin; EMT; Invasion and metastasis; LYMPH-NODE METASTASIS; INVASIVE DUCTAL CARCINOMA; CHEMOKINE RECEPTOR CXCR4; BETA-CATENIN; COLON-CANCER; PANCREATIC-CANCER; BREAST-CANCER; POOR SURVIVAL; WNT PATHWAY; IN-VITRO;

D O I：

10.1016/j.canlet.2014.08.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in angiogenesis and are associated with tumor progression. This study aimed to investigate the role of SDF-1/CXCR4-mediated epithelial-mesenchymal transition (EMT) and the progression of colorectal cancer (CRC) as well as the underlying mechanisms. The data showed that expression of CXCR4 and beta-catenin mRNA and protein was significantly higher in CRC tissues than in distant normal tissues. CXCR4 expression was associated with beta-catenin expression in CRC tissues, whereas high CXCR4 expression was strongly associated with low E-cadherin, high N-cadherin, and high vimentin expression, suggesting a cross talk between the SDF-1/CXCR4 axis and Wnt/beta-catenin signaling pathway in CRC. In vitro, SDF-1 induced CXCR4-positive colorectal cancer cell invasion and EMT by activation of the Wnt/beta-catenin signaling pathway. In contrast, SDF-1/CXCR4 axis activation-induced colorectal cancer invasion and EMT was effectively inhibited by the Wnt signaling pathway inhibitor Dickkopf-1. In conclusion, CXCR4-promoted CRC progression and EMT were regulated by the Wnt/beta-catenin signaling pathway. Thus, targeting of the SDF-1/CXCR4 axis could have clinical applications in suppressing CRC progression. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：417 / 426

页数：10

共 45 条

[1]

CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy [J].