The Interleukin-33/ST2 axis promotes glioma mesenchymal transition, stemness and TMZ resistance via JNK activation

Lin，Lin1,2; Li，Yang1,2; Liu，Mingli1,2; Li，Qingbin1,2; Liu，Quan4; Li，Ruiyan1,2,3

2020-01-31

10.18632/aging.102707

Aging-US   Impact Factor & Quartile

1945-4589

IL-33 is an important member of the IL-1 family which has pleiotropic activities in innate and adaptive immune responses. Recently, some researchers have focused on the function of cellular immunity in the development of tumor. The biological role of IL-33 in glioma is poorly understood. In this study, we showed that glioma cells and tissues expressed higher levels of IL-33 and its receptor ST2 compared to normal brain. Clinically, IL-33 expression was associated with poor survival in patients with glioma. Administration of human IL-33 enhanced cell migration, invasion, epithelial to mesenchymal transition and stemness. Anti-ST2 blocked these effects of IL-33 on tumor. Mechanistically, IL-33 activated JNK signaling pathway via ST2 and increased the expression of key transcription factors that controlled the process of EMT and stemness. Moreover, IL-33 prevented temozolomide induced tumor apoptosis. Anti-ST2 or knockdown IL-33 increased the sensitivity of tumor to temozolomide. Thus, targeting the IL-33/ST2 axis may offer an opportunity to the treatment of glioma patients.

EMT Glioma IL-33 Stemness Temozolomide

English

Corresponding

2-s2.0-85079102579

Scopus

1.Department of Neurosurgery,Second Affiliated Hospital of Harbin Medical University,Harbin,150086,China
2.Chinese Glioma Cooperative Group (CGCG),Beijing,100050,China
3.Neuroscience Institute,Heilongjiang Academy of Medical Sciences,Harbin,150086,China
4.Southern University of Science and Technology,Shenzhen,518055,China

Lin，Lin,Li，Yang,Liu，Mingli,et al. The Interleukin-33/ST2 axis promotes glioma mesenchymal transition, stemness and TMZ resistance via JNK activation[J]. Aging-US,2020,12(2):1685-1703.

Lin，Lin,Li，Yang,Liu，Mingli,Li，Qingbin,Liu，Quan,&Li，Ruiyan.(2020).The Interleukin-33/ST2 axis promotes glioma mesenchymal transition, stemness and TMZ resistance via JNK activation.Aging-US,12(2),1685-1703.

Lin，Lin,et al."The Interleukin-33/ST2 axis promotes glioma mesenchymal transition, stemness and TMZ resistance via JNK activation".Aging-US 12.2(2020):1685-1703.