CXCL5/CXCR2 axis promotes bladder cancer cell migration and invasion by activating PI3K/AKT-induced upregulation of MMP2/MMP9

  • Authors:
    • Ye Gao
    • Zhenfeng Guan
    • Jiaqi Chen
    • Hongjun Xie
    • Zhao Yang
    • Jinhai Fan
    • Xinyang Wang
    • Lei Li
  • View Affiliations

  • Published online on: June 9, 2015     https://doi.org/10.3892/ijo.2015.3041
  • Pages: 690-700
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Abstract

Bladder cancer (BCa) is the most common malignant disease of the urinary tract system, yet the etiology is still poorly understood. Clinically, the majority of BCa patients progress to invasive disease at the final stage, leading to death. Previous investigations have demonstrated that matrix metal­loproteinases (MMPs) play irreplaceable roles in tumor cell extravasation and implantation. In addition, increasing numbers of reports provide evidence that MMPs, especially MMP2 and MMP9 are monitored by various signal transduction pathways targeting tumor metastasis. Seed-and-soil theory has called to attention the importance of the tumor microenvironment in disease progression. To that end, we previously reported the key role of hypoxia in BCa progression. Herein, we report the role of chemokines, specifically CXCL5, is involved in BCa development. Though it has been reported that CXCL5 promotes BCa metastasis and progression, the exact mechanisms are still unknown, necessitating the need for further investigation into the role of CXCL5 in BCa. In this study, IHC staining of BCa tumor sections showed elevated expression of CXCL5 in BCa, which correlated with disease stage. Our mechanistic studies show that CXCL5 contributes to BCa migration and invasion by binding to its receptor, CXCR2, leading to the upregulation of MMP2/MMP9 by activating PI3K/AKT signaling. This study offers vital evidence of how CXCL5 promotes BCa metastasis, and thus may potentially be used as a therapeutic target against BCa.
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August-2015
Volume 47 Issue 2

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

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Spandidos Publications style
Gao Y, Guan Z, Chen J, Xie H, Yang Z, Fan J, Wang X and Li L: CXCL5/CXCR2 axis promotes bladder cancer cell migration and invasion by activating PI3K/AKT-induced upregulation of MMP2/MMP9. Int J Oncol 47: 690-700, 2015
APA
Gao, Y., Guan, Z., Chen, J., Xie, H., Yang, Z., Fan, J. ... Li, L. (2015). CXCL5/CXCR2 axis promotes bladder cancer cell migration and invasion by activating PI3K/AKT-induced upregulation of MMP2/MMP9. International Journal of Oncology, 47, 690-700. https://doi.org/10.3892/ijo.2015.3041
MLA
Gao, Y., Guan, Z., Chen, J., Xie, H., Yang, Z., Fan, J., Wang, X., Li, L."CXCL5/CXCR2 axis promotes bladder cancer cell migration and invasion by activating PI3K/AKT-induced upregulation of MMP2/MMP9". International Journal of Oncology 47.2 (2015): 690-700.
Chicago
Gao, Y., Guan, Z., Chen, J., Xie, H., Yang, Z., Fan, J., Wang, X., Li, L."CXCL5/CXCR2 axis promotes bladder cancer cell migration and invasion by activating PI3K/AKT-induced upregulation of MMP2/MMP9". International Journal of Oncology 47, no. 2 (2015): 690-700. https://doi.org/10.3892/ijo.2015.3041