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Histone serotonylation regulates ependymoma tumorigenesis.
Chen, Hsiao-Chi; He, Peihao; McDonald, Malcolm; Williamson, Michael R; Varadharajan, Srinidhi; Lozzi, Brittney; Woo, Junsung; Choi, Dong-Joo; Sardar, Debosmita; Huang-Hobbs, Emmet; Sun, Hua; Ippagunta, Siri M; Jain, Antrix; Rao, Ganesh; Merchant, Thomas E; Ellison, David W; Noebels, Jeffrey L; Bertrand, Kelsey C; Mack, Stephen C; Deneen, Benjamin.
Afiliación
  • Chen HC; Program in Cancer and Cell Biology, Baylor College of Medicine, Houston, TX, USA.
  • He P; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • McDonald M; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA.
  • Williamson MR; Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX, USA.
  • Varadharajan S; Program in Cancer and Cell Biology, Baylor College of Medicine, Houston, TX, USA.
  • Lozzi B; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • Woo J; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA.
  • Choi DJ; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • Sardar D; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA.
  • Huang-Hobbs E; Program in Development, Disease, Models and Therapeutics, Baylor College of Medicine, Houston, TX, USA.
  • Sun H; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • Ippagunta SM; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA.
  • Jain A; Center of Excellence in Neuro-Oncology Sciences (CENOS), St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Rao G; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • Merchant TE; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA.
  • Ellison DW; Program in Genetics and Genomics, Baylor College of Medicine, Houston, TX, USA.
  • Noebels JL; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • Bertrand KC; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA.
  • Mack SC; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • Deneen B; Center for Cancer Neuroscience, Baylor College of Medicine, Houston, TX, USA.
Nature ; 632(8026): 903-910, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39085609
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Histonas / Ependimoma / Carcinogénesis Límite: Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Histonas / Ependimoma / Carcinogénesis Límite: Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido