PUBLICATION
MOXD1 is a lineage-specific gene and a tumor suppressor in neuroblastoma
- Authors
- Fredlund, E., Andersson, S., Hilgert, E., Monferrer, E., Álvarez-Hernán, G., Karakaya, S., Loontiens, S., Bek, J.W., Gregor, T., Lecomte, E., Magnusson, E., Miltenyte, E., Cabirol, M., Kyknas, M., Engström, N., Henriksson, M.A., Hammarlund, E., Rosenblum, J.S., Noguera, R., Speleman, F., van Nes, J., Mohlin, S.
- ID
- ZDB-PUB-240622-1
- Date
- 2024
- Source
- Science advances 10: eado1583eado1583 (Journal)
- Registered Authors
- Speleman, Frank
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Lineage/genetics
- Gene Expression Regulation, Neoplastic*
- Genes, Tumor Suppressor*
- Humans
- Mice
- Neural Crest/metabolism
- Neural Crest/pathology
- Neuroblastoma*/genetics
- Neuroblastoma*/metabolism
- Neuroblastoma*/pathology
- Schwann Cells/metabolism
- Schwann Cells/pathology
- Zebrafish*/genetics
- PubMed
- 38905335 Full text @ Sci Adv
Citation
Fredlund, E., Andersson, S., Hilgert, E., Monferrer, E., Álvarez-Hernán, G., Karakaya, S., Loontiens, S., Bek, J.W., Gregor, T., Lecomte, E., Magnusson, E., Miltenyte, E., Cabirol, M., Kyknas, M., Engström, N., Henriksson, M.A., Hammarlund, E., Rosenblum, J.S., Noguera, R., Speleman, F., van Nes, J., Mohlin, S. (2024) MOXD1 is a lineage-specific gene and a tumor suppressor in neuroblastoma. Science advances. 10:eado1583eado1583.
Abstract
Neuroblastoma is a childhood developmental cancer; however, its embryonic origins remain poorly understood. Moreover, in-depth studies of early tumor-driving events are limited because of the lack of appropriate models. Herein, we analyzed RNA sequencing data obtained from human neuroblastoma samples and found that loss of expression of trunk neural crest-enriched gene MOXD1 associates with advanced disease and worse outcome. Further, by using single-cell RNA sequencing data of human neuroblastoma cells and fetal adrenal glands and creating in vivo models of zebrafish, chick, and mouse, we show that MOXD1 is a determinate of tumor development. In addition, we found that MOXD1 expression is highly conserved and restricted to mesenchymal neuroblastoma cells and Schwann cell precursors during healthy development. Our findings identify MOXD1 as a lineage-restricted tumor-suppressor gene in neuroblastoma, potentiating further stratification of these tumors and development of novel therapeutic interventions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping