English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse
  1. View item / 
  2. Item Summary

Item

ITEM ACTIONSEXPORT
Add to Basket
  Local TagsRelease HistoryDetailsSummary

Released
Journal Article

Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma

MPS-Authors
/persons/resource/persons215416

Murray,  Peter J.
Murray, Peter / Immunoregulation, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Abu-Zaid, A., Fang, J., Jin, H., Singh, S., Pichavaram, P., Wu, Q., et al. (2024). Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma. Cell Reports Medicine, 5(3): 101468. doi:10.1016/j.xcrm.2024.101468.


Cite as: https://hdl.handle.net/21.11116/0000-000F-51AF-1
Abstract
Neuroblastoma with MYCN amplification (MNA) is a high -risk disease that has a poor survival rate. Neuroblastoma displays cellular heterogeneity, including more differentiated (adrenergic) and more primitive (mesenchymal) cellular states. Here, we demonstrate that MYCN oncoprotein promotes a cellular state switch in mesenchymal cells to an adrenergic state, accompanied by induction of histone lysine demethylase 4 family members (KDM4A-C) that act in concert to control the expression of MYCN and adrenergic core regulatory circulatory (CRC) transcription factors. Pharmacologic inhibition of KDM4 blocks expression of MYCN and the adrenergic CRC transcriptome with genome-wide induction of transcriptionally repressive H3K9me3, resulting in potent anticancer activity against neuroblastomas with MNA by inducing neuroblastic differentiation and apoptosis. Furthermore, a short-term KDM4 inhibition in combination with conventional, cytotoxic chemotherapy results in complete tumor responses of xenografts with MNA. Thus, KDM4 blockade may serve as a transformative strategy to target the adrenergic CRC dependencies in MNA neuroblastomas.