Tumor Biology

, Volume 37, Issue 5, pp 6371–6378 | Cite as

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

  • Jing Guo
  • Xiaofang Yu
  • Jie Gu
  • Zongwu Lin
  • Guangyin Zhao
  • Fengkai Xu
  • Chunlai Lu
  • Di Ge
Original Article


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.


CXCR4 Chemokines Esophageal neoplasms Neoplasm metastasis PI3K/AKT 


Compliance with ethical standards

Conflicts of interest


Grant support

The study was supported by Natural Science Foundation of Ningbo, Zhejiang province, China (No. 2014A610218), National Natural Science Foundation of China (No. 81302099), and ZHU XUE Program of Fudan University.

Supplementary material

13277_2015_4504_Fig7_ESM.gif (25 kb)
Supplementary Figure 1

Western blotting analysis of phosphorylation AKT in Eca109 cell lines and HEEC cell lines (a). Western blotting analysis of phosphorylation AKT, RhoA, Rac-1, and Cdc42 in HEEC cells, HEEC-vector cells, and HEEC-CXCR4 cells (b). (GIF 24 kb)

13277_2015_4504_MOESM1_ESM.tif (846 kb)
High resolution image (TIF 846 kb)
13277_2015_4504_Fig8_ESM.gif (70 kb)
Supplementary Figure 2

Expression of CXCR4 in Eca109 with gene downregulation (a). Western blotting analysis of phosphorylation AKT, RhoA, Rac-1, and Cdc42 in Eca109/shCtl cells, Eca109/shCXCR4 cells, and Eca109/shCXCR4-AKT cells (b). The growth curves for Eca109/shCtl cells, Eca109/shCXCR4 cells, and Eca109/shCXCR4-AKT cells in vitro proliferation assays (c). Results of transwell assays showed the representative images of invasive Eca109/shCtl cells, Eca109/shCXCR4 cells, and Eca109/shCXCR4-AKT cells (d). (GIF 70 kb)

13277_2015_4504_MOESM2_ESM.tif (2.2 mb)
High resolution image (TIF 2227 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Thoracic SurgeryNingbo No.1 HospitalNingboChina
  2. 2.Department of Nephrology, Zhongshan HospitalFudan UniversityShanghaiChina
  3. 3.Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
  4. 4.Shanghai No.1 HospitalShanghai Jiao Tong UniversityShanghaiChina

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