Glioma proteome - Quantitative proteomics reveals fundamental regulatory differences in oncogenic HRAS and IDH1 driven astrocytoma

ABSTRACT: In the present study, we applied a quantitative MS-based strategy to characterize the proteome and phosphoproteome in HRAS- or IDH1-driven glioma cells. We describe the driving roles of the MEK and PI3K signaling pathways in RAS-NHA cells, and uncover oncogenic signaling in other pathways. We highlight the interplay between the signaling cascades and show that inhibition of MEK and PI3K reverses phosphorylation signaling patterns driven by oncogenic RAS overexpression. Applying a histone hybrid chemical labeling method and high-resolution MS, we identified significant histone methylation, acetylation, and butyrylation changes in IDH1mut-NHA cells. Our results suggest a global transcriptional repressive state, consistent with the down-regulation of the proteome, transcriptome, and the DNA hyper-methylated state in IDH1mut-NHA cells. We provide a unique resource of altered proteins, phosphosites, and histone PTMs in RAS and IDH1 mutant astrocytoma cell lines, providing insight into oncogenesis in glioma beyond the transcriptomic level.

INSTRUMENT(S): LTQ Orbitrap Velos, Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Sophia Doll  

LAB HEAD: Sophia Doll

PROVIDER: PXD004945 | Pride | 2016-12-23

REPOSITORIES: Pride