SDF-1/CXCR4 signaling induces pancreatic cancer cell invasion and epithelial-mesenchymal transition in vitro through non-canonical activation of Hedgehog pathway

被引：164

作者：

Li, Xuqi ^{[1
]}

Ma, Qingyong ^{[1
]}

Xu, Qinhong ^{[1
]}

Liu, Han ^{[1
]}

Lei, Jianjun ^{[1
]}

Duan, Wanxing ^{[1
]}

Bhat, Kruttika ^{[2
]}

Wang, Fengfei ^{[2
]}

Wu, Erxi ^{[2
]}

Wang, Zheng ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Xian 710061, Shaanxi, Peoples R China

[2] N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58105 USA

来源：

CANCER LETTERS | 2012年 / 322卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CXCR4; Hedgehog pathway; Pancreatic cancer invasion; Epithelial-mesenchymal transition; CHEMOKINE RECEPTOR CXCR4; EXPRESSION; MIGRATION; BLOCKADE;

D O I：

10.1016/j.canlet.2012.02.035

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

In our previous study, we found that blockade of SDF-1/CXCR4 signaling inhibits pancreatic cancer cell migration and invasion in vitro. However, the mechanism governing the downstream regulation of SDF-1/CXCR4-mediated invasion remains unclear. Here we report the role of SDF-1/CXCR4 in pancreatic cancer and the possible mechanism of SDF-1/CXCR4-mediated pancreatic cancer invasion. We show that there is a cross-talk between SDF-1/CXCR4 axis and non-canonical Hedgehog (Hh) pathway in pancreatic cancer. Furthermore, our data demonstrate that the ligand of CXCR4, SDF-1 induces CXCR4-positive pancreatic cancer invasion, epithelial-mesenchymal transition (EMT) process and activates the non-canonical Hh pathway. Moreover, we also demonstrate that the invasion of a pancreatic cancer and EMT resulting from the activation of SDF-1/CXCR4 axis is effectively inhibited by Smoothened (SMO) inhibitor cyclopamine and siRNA specific to Gli-1. Collectively, these data demonstrate that SDF-1/CXCR4 modulates the non-canonical Hh pathway by increasing the transcription of SMO in a ligand-independent manner. Taken together, SDF-1/CXCR4 axis may represent a promising therapeutic target to prevent pancreatic cancer progression. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：169 / 176

页数：8

共 29 条

[1]

Sonic hedgehog paracrine signaling regulates metastasis and lymphangiogenesis in pancreatic cancer [J].