Macrophage migration inhibitory factor enhances autophagy by regulating ROCK1 activity and contributes to the escape of dendritic cell surveillance in glioblastoma.
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.
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Shugang
S
Xu
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Xing
X
Guo
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Xiao
X
Gao
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Hao
H
Xue
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Jinsen
J
Zhang
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Xiaofan
X
Guo
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Wei
W
Qiu
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Ping
P
Zhang
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Gang
G
Li
D001343:Autophagy; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
D008263:Macrophage Migration-Inhibitory Factors; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human