MOXD1 is a gate-keeper of organ homeostasis and functions as a tumor-suppressor in neuroblastoma
biorxiv(2023)
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 Summary Neural crest-specific MOXD1 is a de novo tumor-suppressor gene in childhood cancers arising during embryogenesis.
### Competing Interest Statement
The authors have declared no competing interest.
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Key words
tumor-suppressor tumor-suppressor,organ homeostasis,gate-keeper
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