CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming
Source abstract
Abstract
Abstract Neuroblastoma (NB) arises from oncogenic disruption of neural crest (NC) differentiation. Treatment with retinoic acid (RA) to induce differentiation has improved survival in some NB patients, but not all patients respond, and most NBs eventually develop resistance to RA. Loss of the chromatin modifier chromatin assembly factor 1 subunit p150 (CHAF1A) promotes NB cell differentiation; however, the mechanism by which CHAF1A drives NB oncogenesis has remained unexplored. This study shows that CHAF1A gain‐of‐function supports cell malignancy, blocks neuronal differentiation in three models (zebrafish NC, human NC, and human NB), and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression. Targeting polyamine synthesis promotes NB differentiation and enhances the anti‐tumor activity of RA. The authors' results provide insight into the mechanisms that drive NB oncogenesis and suggest a rapidly translatable therapeutic approach (DFMO plus RA) to enhance the clinical efficacy of differentiation therapy in NB patients.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Neuroblastoma Research and Treatments · Glioma Diagnosis and Treatment · Cancer, Hypoxia, and Metabolism
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Pediatrics Section of Hematology‐Oncology Texas Children's Cancer and Hematology Centers Baylor College of Medicine Houston TX 77030 USA
Dan L Duncan Comprehensive Cancer Center Baylor College of Medicine Houston TX 77030 USA
Department of BioSciences Rice University Houston TX 77005 USA
Department of Pharmacy and Biotechnology University of Bologna Bologna 40126 Italy
Stem Cells and Regenerative Medicine Center Center for Cell and Gene Therapy Baylor College of Medicine Houston TX 77030 USA
Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX 77030 USA
Program in Developmental Biology Baylor College of Medicine Houston TX 77030 USA
Advanced Technology Core Baylor College of Medicine Houston TX 77030 USA
Department of Pathology and Immunology Texas Children’s Hospital, Baylor College of Medicine Houston TX 77030 USA
Division of Pediatric Surgery Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston TX 77030 USA
Center for Precision Environmental Health Baylor College of Medicine Houston TX 77030 USA
Funding
National Institutes of Health · Cancer Prevention and Research Institute of Texas · American Cancer Society · Associazione Italiana per la Ricerca sul Cancro · Dan L. Duncan Cancer Center, Baylor College of Medicine · St. Baldrick's Foundation · Andrew McDonough B+ Foundation
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