Macrophage migration inhibitory factor enhances autophagy by regulating ROCK1 activity and contributes to the escape of dendritic cell surveillance in glioblastoma

  • Authors:
    • Shugang Xu
    • Xing Guo
    • Xiao Gao
    • Hao Xue
    • Jinsen Zhang
    • Xiaofan Guo
    • Wei Qiu
    • Ping Zhang
    • Gang Li
  • View Affiliations

  • Published online on: September 23, 2016     https://doi.org/10.3892/ijo.2016.3704
  • Pages: 2105-2115
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Macrophage migration inhibitory factor (MIF) is highly expressed in glioblastoma, promoting malignant progression and suppresses immune surveillance. However, the mechanism underlying its biological roles in human glioblastoma and the capability of MIF to escape dendritic cell (DC) surveillance remain poorly understood. In the present study, we found that recombinant human MIF (rhMIF) activated the RhoA‑ROCK1 pathway and simultaneously upregulated F‑actin fibre formation. Additionally, we showed that rhMIF increased autophagy in glioblastoma cells, and knockdown of endogenic MIF suppressed autophagy. In glioma specimens, MIF expression was significantly correlated with LC3B levels. Moreover, we confirmed that the activity of Rho‑associated coiled‑coil containing kinase (ROCK)1 played a crucial role in MIF‑induced autophagy. Y26736, a ROCK1 inhibitor, blocked the MIF‑mediated increase in migration and colony formation in glioblastoma multiforme (GBM) cells. Furthermore, exogenous rhMIF suppressed the migration of both immature DCs (iDCs) and mature DCs (mDCs). Addition of rhMIF during the maturation process of iDCs impaired the expression of co‑stimulatory markers. Taken together, our results identified ROCK1 as a critical mediator of MIF‑induced autophagy and the immunosuppressive effect of MIF on DC surveillance in glioblastoma.
View Figures
View References

Related Articles

Journal Cover

November-2016
Volume 49 Issue 5

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Xu S, Guo X, Gao X, Xue H, Zhang J, Guo X, Qiu W, Zhang P and Li G: Macrophage migration inhibitory factor enhances autophagy by regulating ROCK1 activity and contributes to the escape of dendritic cell surveillance in glioblastoma. Int J Oncol 49: 2105-2115, 2016.
APA
Xu, S., Guo, X., Gao, X., Xue, H., Zhang, J., Guo, X. ... Li, G. (2016). Macrophage migration inhibitory factor enhances autophagy by regulating ROCK1 activity and contributes to the escape of dendritic cell surveillance in glioblastoma. International Journal of Oncology, 49, 2105-2115. https://doi.org/10.3892/ijo.2016.3704
MLA
Xu, S., Guo, X., Gao, X., Xue, H., Zhang, J., Guo, X., Qiu, W., Zhang, P., Li, G."Macrophage migration inhibitory factor enhances autophagy by regulating ROCK1 activity and contributes to the escape of dendritic cell surveillance in glioblastoma". International Journal of Oncology 49.5 (2016): 2105-2115.
Chicago
Xu, S., Guo, X., Gao, X., Xue, H., Zhang, J., Guo, X., Qiu, W., Zhang, P., Li, G."Macrophage migration inhibitory factor enhances autophagy by regulating ROCK1 activity and contributes to the escape of dendritic cell surveillance in glioblastoma". International Journal of Oncology 49, no. 5 (2016): 2105-2115. https://doi.org/10.3892/ijo.2016.3704