Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in colorectal cancer through ERK and β-arrestin pathways

  • Authors:
    • Xin-Xiang Li
    • Hong-Tu Zheng
    • Li-Yong Huang
    • De-Bing Shi
    • Jun-Jie Peng
    • Lei Liang
    • San-Jun Cai
  • View Affiliations

  • Published online on: July 21, 2014     https://doi.org/10.3892/ijo.2014.2547
  • Pages: 1649-1657
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Abstract

The CXC chemokine receptor 7 (CXCR7) has been reported to be involved in cell growth, metastasis and apoptosis in certain cancers. However, the function and molecular mechanisms of CXCR7 in human colorectal cancer (CRC) are still undefined. In the present study, sixty-eight cases of CRC tissues and corresponding adjacent non-cancer tissues (ANCT) were collected, and the expression of CXCR7 was assessed using immunohistochemistry (IHC) in biopsy samples. Furthermore, CXCR7 gene was silenced by small hairpin RNA-mediated lentiviral vector (Lv-shCXCR7), by transfection into human CRC cells (SW480 and HT-29). The levels of p-ERK, β-arrestin, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2) and caspase-3 (CAS-3) were detected by western blotting. Cell proliferative activities and invasive capability were respectively measured by MTT and Transwell assays. Cell apoptosis was analyzed by flow cytometry. The results demonstrated that CXCR7 expression was significantly upregulated in CRC tissues compared with the ANCT (54.4 vs. 36.8%, P=0.041), and correlated with Dukes staging and depth of invasion (P=0.007; P=0.002). Silencing of CXCR7 gene suppressed cell proliferation and invasion, and induced cell apoptosis in CRC cells with decreased expression of p-ERK, β-arrestin, PCNA and MMP-2 but increased expression of CAS-3. The tumor volumes in the SW480 subcutaneous tumor models treated with Lv-shCXCR7 were significantly smaller than those of the negative control (NC) and PBS groups (P<0.01). In conclusion, our findings indicate that upregulation of CXCR7 expression is associated with tumor invasion, and silencing of the CXCR7 gene represses the development of CRC cells through ERK and β-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of CRC.
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October 2014
Volume 45 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Li X, Zheng H, Huang L, Shi D, Peng J, Liang L and Cai S: Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in colorectal cancer through ERK and β-arrestin pathways. Int J Oncol 45: 1649-1657, 2014
APA
Li, X., Zheng, H., Huang, L., Shi, D., Peng, J., Liang, L., & Cai, S. (2014). Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in colorectal cancer through ERK and β-arrestin pathways. International Journal of Oncology, 45, 1649-1657. https://doi.org/10.3892/ijo.2014.2547
MLA
Li, X., Zheng, H., Huang, L., Shi, D., Peng, J., Liang, L., Cai, S."Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in colorectal cancer through ERK and β-arrestin pathways". International Journal of Oncology 45.4 (2014): 1649-1657.
Chicago
Li, X., Zheng, H., Huang, L., Shi, D., Peng, J., Liang, L., Cai, S."Silencing of CXCR7 gene represses growth and invasion and induces apoptosis in colorectal cancer through ERK and β-arrestin pathways". International Journal of Oncology 45, no. 4 (2014): 1649-1657. https://doi.org/10.3892/ijo.2014.2547