胶质母细胞瘤（GBM）是一种最致命的肿瘤之一，表现出高度浸润性表型。在这里，我们确定了共同调控GBM侵袭相关基因的转录因子（TF）。利用基于胶原的三维侵袭试验定量测定了肿瘤球（TS）的浸润能力。利用GBM转录组进行丰富分析量化了TF的活性，并通过细胞放大的蛋白质组成像分析进行了确认。使用siRNA或shRNA敲低侵袭相关TF，并将TS正位植入小鼠体内。将23例来源于患者的GBM TS分为低侵袭组和高侵袭组后，我们确定了每组中的活跃TF，[对于]低侵袭组是PCBP1，而对于高侵袭组是STAT3和SRF。敲低这些TF逆转了GBM TS的表型和侵袭标记物表达。值得注意的是，MRI揭示了TS和起源肿瘤之间一致的浸润模式，高浸润性与不良预后有关。与对照组相比，植入STAT3或SRF敲低GBM TS的小鼠显示出减少正常组织浸润和肿瘤生长以及延长生存的结果，表明存在治疗反应。我们的综合转录组分析在GBM中确定了三个侵袭相关TF。基于转录程序、侵袭表型和预后之间的关系，我们认为这些TF是GBM治疗的潜在靶点。© 2023. 作者(s)。

Glioblastoma (GBM), one of the most lethal tumors, exhibits a highly infiltrative phenotype. Here, we identified transcription factors (TFs) that collectively modulate invasion-related genes in GBM.The invasiveness of tumorspheres (TSs) were quantified using collagen-based 3D invasion assays. TF activities were quantified by enrichment analysis using GBM transcriptome, and confirmed by cell-magnified analysis of proteome imaging. Invasion-associated TFs were knocked down using siRNA or shRNA, and TSs were orthotopically implanted into mice.After classifying 23 patient-derived GBM TSs into low- and high-invasion groups, we identified active TFs in each group-PCBP1 for low invasion, and STAT3 and SRF for high invasion. Knockdown of these TFs reversed the phenotype and invasion-associated-marker expression of GBM TSs. Notably, MRI revealed consistent patterns of invasiveness between TSs and the originating tumors, with an association between high invasiveness and poor prognosis. Compared to controls, mice implanted with STAT3- or SRF-downregulated GBM TSs showed reduced normal tissue infiltration and tumor growth, and prolonged survival, indicating a therapeutic response.Our integrative transcriptome analysis revealed three invasion-associated TFs in GBM. Based on the relationship among the transcriptional program, invasive phenotype, and prognosis, we suggest these TFs as potential targets for GBM therapy.© 2023. The Author(s).