The PTPRZ1-MET/STAT3/ISG20 axis in glioma stem-like cells modulates tumor-associated macrophage polarization

In this study, we analyzed RNA-seq data from sGBM patients' glioma tissues with or without ZM fusion,and found that stemness and macrophage markers were more highly expressed in sGBM patients harboring ZM than in those without ZM fusion. ZM enhanced the self-renewal and proliferation of GSCs, thereby accelerating glioma progression. In addition, ZM-positive GSCs facilitated the infiltration of TAMs and drove their polarization toward an immunosuppressive phenotype, which was primarily accomplished through the extracellular secretion of ISG20. Our research identified the MET-STAT3-ISG20 axis within GSCs, thus demonstrating the critical role of ZM in GBM initiation and progression. Our study demonstrated that, in contrast to ZM-positive differentiated glioma cells, ZM-positive GSCs upregulated ISG20 expression through the MET-STAT3-ISG20 axis. The extracellular secretion of ISG20 recruited and induced M2-like polarization in macrophages, thereby promoting tumor progression. Our results reveal a novel mechanism involved in ZM-positive GBM pathogenesis and identify potential therapeutic targets.PMID:38685521 | DOI:10.1016/j.cellsig.2024.111191

Source: Cellular Signalling - April 30, 2024 Category: Cytology Authors: Yuxin Wang Jinghao Suo Zhixing Wang Kunnian Ran Yuan Tian Wei Han Yanwei Liu Xiaozhong Peng Source Type: research