Proteomics

Dataset Information

0

GSC 2907 SRGN IP mass spectrometry


ABSTRACT: Glioblastoma (GBM) is a highly lethal primary malignant brain tumor. The high level of heterogeneity within GBM inevitably leads to treatment resistance and tumor recurrence. Glioblastoma stem cells (GSCs) contribute to the distinct properties of GBM through their contribution to therapeutic resilience. Here, we found that enhanced classical (CL) and mesenchymal (MES) transcriptional signatures were associated with poor patient prognosis. Through the integrated analyses of single-cell RNA sequencing and clinical datasets, we identified specific brain tumor targets, including MEOX2 for the CL subtype and SRGN for the MES subtype respectively. MEOX2 sustained the CL subtype signature and played a particular role in CL GSCs by activating Notch signaling. SRGN maintained the MES phenotype and regulated the NF-κB signaling by preventing NFKB1 from proteasomal degradation. Both genetic and pharmacologic treatments showed that CL GSCs were preferentially sensitive to the inhibition of MEOX2, while MES GSCs were more susceptible to SRGN. We further screend FDA-approved drugs with MEOX2 and SRGN targeting capabilities as candidates for further investigation. Combined CL and MES targeting demonstrated enhanced efficacy, both in vitro and in vivo. Collectively, our results elucidated the mechanism of GBM heterogeneity, and highlighted a therapeutic strategy for the elimination of heterogeneous cellular populations through combinatorial targeting of MEOX2 and SRGN in GSCs.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Xiuxing Wang  

LAB HEAD: Xiuxing Wang

PROVIDER: PXD061009 | Pride | 2025-05-07

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
2907.raw Raw
IgG.dat Other
IgG.raw Raw
SRGN.dat Other
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Publications

Combined targeting of glioblastoma stem cells of different cellular states disrupts malignant progression.

Lu Chenfei C   Kang Tao T   Zhang Junxia J   Yang Kailin K   Liu Yang Y   Song Kefan K   Lin Qiankun Q   Dixit Deobrat D   Gimple Ryan C RC   Zhang Qian Q   Shi Zhumei Z   Fan Xiao X   Wu Qiulian Q   Li Daqi D   Shan Danyang D   Gao Jiancheng J   Gu Danling D   You Hao H   Li Yangqing Y   Yang Junlei J   Zhao Linjie L   Qiu Zhixin Z   Yang Hui H   Zhao Ningwei N   Gao Wei W   Tao Weiwei W   Lu Yingmei Y   Chen Yun Y   Ji Jing J   Zhu Zhe Z   Kang Chunsheng C   Man Jianghong J   Agnihotri Sameer S   Wang Qianghu Q   Lin Fan F   Qian Xu X   Mack Stephen C SC   Hu Zhibin Z   Li Chaojun C   Taylor Michael D MD   Liu Ning N   Zhang Nu N   Lu Ming M   You Yongping Y   Rich Jeremy N JN   Zhang Wei W   Wang Xiuxing X  

Nature communications 20250326 1


Glioblastoma (GBM) is the most lethal primary brain tumor with intra-tumoral hierarchy of glioblastoma stem cells (GSCs). The heterogeneity of GSCs within GBM inevitably leads to treatment resistance and tumor recurrence. Molecular mechanisms of different cellular state GSCs remain unclear. Here, we find that classical (CL) and mesenchymal (MES) GSCs are enriched in reactive immune region and high CL-MES signature informs poor prognosis in GBM. Through integrated analyses of GSCs RNA sequencing  ...[more]

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