SUMOylation modification of HNRNPK at the K422 site promotes invasion in glioblastoma
Wenguo Zhao, Jiazheng Wang, Feihu Zhao, Yaquan Li, Zhuo Li, Xingang Li, Anjing Chen
Abstract
Glioblastoma multiforme (GBM) is a highly heterogeneous brain tumor with limited treatment options. Recent studies revealed cellular heterogeneity and the potential for interconversion between distinct cell types on the basis of RNA sequencing and single-cell analyses. The ability of different cell types to adapt to their surrounding environment and undergo transformation significantly complicates the study and treatment of GBM. In this study, we reveal that HNRNPK-SUMO1 expression is predominantly found in the GBM infiltration area. SUMOylation of the K422 residue of HNRNPK interferes with its DNA binding ability, thereby disrupting downstream transcription, and ultimately leading to transitions between different states of glioblastoma stem cells. Although the proneural subtype is considered to have a better prognosis, transitioning towards this state promotes tumor invasion. These findings serve as a reminder to exercise caution when considering treatments targeting specific cellular subtypes.