Open Access

G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway

  • Authors:
    • Qiao Zhang
    • Qiaoqiao Han
    • Zhe Yang
    • Yueli Ni
    • Yannick Luther Agbana
    • Honggang Bai
    • Zihan Yi
    • Xiaojia Yi
    • Yingmin Kuang
    • Yuechun Zhu
  • View Affiliations

  • Published online on: April 8, 2020     https://doi.org/10.3892/ijo.2020.5041
  • Pages: 197-212
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Glucose‑6‑phosphate dehydrogenase (G6PD) is crucial rate‑limiting enzyme of the pentose phosphate pathway (PPP). G6PD dysregulation has been reported in various types of human cancer, and the role of G6PD in cancer progression was demonstrated in numerous studies. A previous study from our laboratory described the prognostic significance of G6PD in clear cell renal cell carcinoma (ccRCC), and demonstrated its proliferative role through positive feedback regulation of the phosphorylated form of signal transducer and activator of transcription 3. However, the role of G6PD in ccRCC invasion remains unclear. In the present study, reverse transcription‑quantitative (RT‑q) PCR, western blotting, enzyme activity assay, transwell assay and immunohistochemistry analysis in cell model, xenograft mice model and human specimen studies were performed to evaluate the role of G6PD in ccRCC invasion. The results from the present study demonstrated that G6PD may promote ccRCC cell invasive ability by increasing matrix metalloproteinase 2 (MMP2) mRNA and protein expression both in vitro and in vivo. In addition, a positive correlation between G6PD and MMP2 expression was demonstrated by RT‑qPCR and western blotting in twenty pairs of ccRCC tumor specimens and matched adjacent normal tissues. Furthermore, G6PD promoted reactive oxygen species (ROS) generation and activated the MAPK signaling pathway in ccRCC cells. In addition, ROS significantly promoted the MAPK signaling pathway activation, which in turn contributed to MMP2 overexpression in ccRCC cells. In conclusion, the present study demonstrated that G6PD may facilitate ccRCC cell invasive ability by enhancing MMP2 expression through ROS‑MAPK axis pathway.

Related Articles

Journal Cover

July 2020
Volume 57 Issue 1

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Zhang, Q., Han, Q., Yang, Z., Ni, Y., Agbana, Y.L., Bai, H. ... Zhu, Y. (2020). G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway. International Journal of Oncology, 57, 197-212. https://doi.org/10.3892/ijo.2020.5041
MLA
Zhang, Q., Han, Q., Yang, Z., Ni, Y., Agbana, Y. L., Bai, H., Yi, Z., Yi, X., Kuang, Y., Zhu, Y."G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway". International Journal of Oncology 57.1 (2020): 197-212.
Chicago
Zhang, Q., Han, Q., Yang, Z., Ni, Y., Agbana, Y. L., Bai, H., Yi, Z., Yi, X., Kuang, Y., Zhu, Y."G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway". International Journal of Oncology 57, no. 1 (2020): 197-212. https://doi.org/10.3892/ijo.2020.5041