Proteomics

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Histone serotonylation regulates ependymoma tumorigenesis through neurodevelopmental pathways

ABSTRACT: Bidirectional communication between tumors and neurons has emerged as a key facet of the tumor microenvironment that drives malignancy. Another hallmark feature of cancer is epigenomic dysregulation, where alterations in gene expression influences cell states and interactions with the tumor microenvironment. Using the pediatric brain tumor ependymoma (EPN) as a model, we found that inhibition of histone serotonylation blocks EPN tumorigenesis and regulates expression of a core set of developmental transcription factors (TFs). High-throughput, in vivo screening of these TFs revealed that ETV5 promotes EPN tumorigenesis and functions by enhancing repressive chromatin states. Neuropeptide Y (NPY) is amongst the genes repressed by ETV5 and its overexpression suppresses EPN tumor progression and tumor-associated network hyperactivity via synaptic remodeling. Collectively, these studies identify histone serotonylation as a key driver of EPN tumorigenesis, while further revealing how neuronal signaling, neuro-epigenomics, and developmental programs are intertwined to drive malignancy in brain cancer.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Antrix Jain  

LAB HEAD: Benjamin Deneen

PROVIDER: PXD048170 | Pride | 2024-09-09

REPOSITORIES: Pride

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48883_1_00F_777_mouse_NT_preclear_band1.msf Msf
48883_1_00F_777_mouse_NT_preclear_band1.raw Raw
48883_1_00F_777_mouse_NT_preclear_band1_TargetPeptideSpectrumMatch.txt Txt
48883_1_00F_777_mouse_NT_preclear_band2_3_4.msf Msf
48883_1_00F_777_mouse_NT_preclear_band2_3_4.raw Raw
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Publications

Bidirectional communication between tumours and neurons has emerged as a key facet of the tumour microenvironment that drives malignancy<sup>1,2</sup>. Another hallmark feature of cancer is epigenomic dysregulation, in which alterations in gene expression influence cell states and interactions with the tumour microenvironment<sup>3</sup>. Ependymoma (EPN) is a paediatric brain tumour that relies on epigenomic remodelling to engender malignancy<sup>4,5</sup>; however, how these epigenetic mechani  ...[more]

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