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MOXD1 is a gate-keeper of organ homeostasis and functions as a tumor-suppressor in neuroblastoma

Fredlund, E.; Andersson, S.; Hilgert, E.; Alvarez-Hernan, G.; Monferrer, E.; Karakaya, S.; Gregor, T.; Loontiens, S.; Bek, J. W.; Lecomte, E.; Magnusson, E.; Miltenyte, E.; Cabirol, M.; Kyknas, M.; Engstrom, N.; Arsenian Henriksson, M.; Hammarlund, E.; Noguera, R.; Speleman, F.; van Nes, J.; Mohlin, S.

2023-01-19 cancer biology
10.1101/2023.01.17.524367 bioRxiv
Show abstract

Neuroblastoma is a childhood cancer believed to result from dysfunctional development. Its origin during embryogenesis remains poorly understood. The lack of appropriate models has hindered in-depth mapping of tumor-driving events. Here, we identify a novel tumor-suppressor gene that predicts poor survival in high-risk disease, by applying bulk and single cell RNA sequencing data of neuroblastoma and human fetal adrenal glands. Trunk neural crest-specific MOXD1 discriminates cell populations during normal and tumor development, with implications for deciphering neuroblastoma cell origin. We created an embryonic conditional knockout model and show that cell type-specific loss of MOXD1 leads to disrupted organ homeostasis and failed adrenal gland formation, home for neuroblastoma. We show that MOXD1 is a tumor suppressor gene in zebrafish, chick, and mice in vivo models. One-Sentence SummaryNeural crest-specific MOXD1 is a de novo tumor-suppressor gene in childhood cancers arising during embryogenesis.

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