2. Academic Validation
  3. Histone serotonylation regulates ependymoma tumorigenesis

Histone serotonylation regulates ependymoma tumorigenesis

  • Nature. 2024 Aug;632(8026):903-910. doi: 10.1038/s41586-024-07751-z.
Hsiao-Chi Chen 1 2 3 4,  Peihao He 1 2 3,  Malcolm McDonald 2 3 5,  Michael R Williamson 2 3,  Srinidhi Varadharajan 6,  Brittney Lozzi 2 3 7,  Junsung Woo 2 3,  Dong-Joo Choi 2 3,  Debosmita Sardar 2 3,  Emmet Huang-Hobbs 2 3 4,  Hua Sun 6,  Siri M Ippagunta 6,  Antrix Jain 8,  Ganesh Rao 3 9,  Thomas E Merchant 10,  David W Ellison 11,  Jeffrey L Noebels 12 13,  Kelsey C Bertrand 14,  Stephen C Mack 15 16 17,  Benjamin Deneen 18 19 20 21 22 23
Affiliations

Affiliations

  • 1 Program in Cancer and Cell Biology, Baylor College of Medicine, Houston, TX, USA.
  • 2 Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • 3 Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA.
  • 4 Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX, USA.
  • 5 Program in Development, Disease, Models and Therapeutics, Baylor College of Medicine, Houston, TX, USA.
  • 6 Center of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA.
  • 7 Program in Genetics and Genomics, Baylor College of Medicine, Houston, TX, USA.
  • 8 Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, USA.
  • 9 Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.
  • 10 Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • 11 Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • 12 Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX, USA.
  • 13 Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
  • 14 Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • 15 Center of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA. stephen.mack@stjude.org.
  • 16 Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA. stephen.mack@stjude.org.
  • 17 Neurobiology and Brain Tumor Program, St Jude Children's Research Hospital, Memphis, TN, USA. stephen.mack@stjude.org.
  • 18 Program in Cancer and Cell Biology, Baylor College of Medicine, Houston, TX, USA. deneen@bcm.edu.
  • 19 Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA. deneen@bcm.edu.
  • 20 Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA. deneen@bcm.edu.
  • 21 Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX, USA. deneen@bcm.edu.
  • 22 Program in Development, Disease, Models and Therapeutics, Baylor College of Medicine, Houston, TX, USA. deneen@bcm.edu.
  • 23 Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA. deneen@bcm.edu.
PMID: 39085609 DOI: 10.1038/s41586-024-07751-z
Abstract

Bidirectional communication between tumours and neurons has emerged as a key facet of the tumour microenvironment that drives malignancy1,2. Another hallmark feature of Cancer is epigenomic dysregulation, in which alterations in gene expression influence cell states and interactions with the tumour microenvironment3. Ependymoma (EPN) is a paediatric brain tumour that relies on epigenomic remodelling to engender malignancy4,5; however, how these epigenetic mechanisms intersect with extrinsic neuronal signalling during EPN tumour progression is unknown. Here we show that the activity of serotonergic neurons regulates EPN tumorigenesis, and that serotonin itself also serves as an activating modification on histones. We found that inhibiting histone serotonylation blocks EPN tumorigenesis and regulates the expression of a core set of developmental transcription factors. High-throughput, in vivo screening of these transcription factors revealed that ETV5 promotes EPN tumorigenesis and functions by enhancing repressive chromatin states. Neuropeptide Y (NPY) is one of the genes repressed by ETV5, and its overexpression suppresses EPN tumour progression and tumour-associated network hyperactivity through synaptic remodelling. Collectively, this study identifies histone serotonylation as a key driver of EPN tumorigenesis, and also reveals how neuronal signalling, neuro-epigenomics and developmental programs are intertwined to drive malignancy in brain Cancer.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z