Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China.
Jinan Microecological Biomedicine Shandong Laboratory and Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan, 250017, China.
Int J Biol Sci. 2024 Oct 21;20(14):5715-5730. doi: 10.7150/ijbs.102051. eCollection 2024.
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.
多形性胶质母细胞瘤（GBM）是一种高度异质性的脑肿瘤，治疗选择有限。最近的研究基于 RNA 测序和单细胞分析揭示了细胞异质性和不同细胞类型之间相互转化的潜力。不同细胞类型适应周围环境并发生转化的能力，极大地增加了 GBM 的研究和治疗的复杂性。在这项研究中，我们揭示了 HNRNPK-SUMO1 的表达主要存在于 GBM 浸润区。HNRNPK 的 K422 残基的 SUMO 化干扰了其 DNA 结合能力，从而破坏了下游转录，最终导致胶质母细胞瘤干细胞的不同状态之间的转变。尽管前神经型亚型被认为具有更好的预后，但向这种状态的转变会促进肿瘤侵袭。这些发现提醒人们在考虑针对特定细胞亚型的治疗方法时要谨慎。
