HSPD1 promotes neuroblastoma by augmenting MYCN expression
- 1Ben Gurion University of the Negev
Abstract
MYCN amplification is associated with poor outcomes in neuroblastoma (NB). MYCN encodes a transcription factor that induces the expression of mitochondrial one-carbon enzymes and chaperones, promoting metabolic reprogramming and aggressiveness in NB tumor cells. While the contribution of MYCN to changes in the mitochondrial proteome is well established, how mitochondrial proteostasis contributes to MYCN activity remains poorly understood. Mitochondrial HSP60 (HSPD1) is a conserved mitochondrial chaperone promoting the mitochondrial one-carbon pathway and mitochondrial translation by folding the one-carbon enzyme MTHFD2 and preventing aggregation of mitochondrial ribosomal proteins. Here, we show that HSPD1 depletion in MYCN-amplified NB cells led to reduced mitochondrial translation, MYCN expression, and tumorigenesis in vitro and in vivo. In addition, HSPD1 mRNA and protein correlate with MYCN expression in NB tumors. These results establish HSPD1 as a promising target for the treatment of MYCN-amplified NB.
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BibTeX
@misc{alassam2026hspd1,
title = {{HSPD1 promotes neuroblastoma by augmenting MYCN expression}},
author = {S. S. Alassam and D. B. Manikandan and H. Ben-David and L. Cohen and S. Kaluski-Kopatch and L. Hruby and S. Dror and P. H. Sorensen and A. Delaidelli and G. Leprivier and M. Elkabets and B. Rotblat},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749066},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749066v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - HSPD1 promotes neuroblastoma by augmenting MYCN expression
AU - S. S. Alassam
AU - D. B. Manikandan
AU - H. Ben-David
AU - L. Cohen
AU - S. Kaluski-Kopatch
AU - L. Hruby
AU - S. Dror
AU - P. H. Sorensen
AU - A. Delaidelli
AU - G. Leprivier
AU - M. Elkabets
AU - B. Rotblat
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749066
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749066v1
AB - MYCN amplification is associated with poor outcomes in neuroblastoma (NB). MYCN encodes a transcription factor that induces the expression of mitochondrial one-carbon enzymes and chaperones, promoting metabolic reprogramming and aggressiveness in NB tumor cells. While the contribution of MYCN to changes in the mitochondrial proteome is well established, how mitochondrial proteostasis contributes to MYCN activity remains poorly understood. Mitochondrial HSP60 (HSPD1) is a conserved mitochondrial chaperone promoting the mitochondrial one-carbon pathway and mitochondrial translation by folding the one-carbon enzyme MTHFD2 and preventing aggregation of mitochondrial ribosomal proteins. Here, we show that HSPD1 depletion in MYCN-amplified NB cells led to reduced mitochondrial translation, MYCN expression, and tumorigenesis in vitro and in vivo. In addition, HSPD1 mRNA and protein correlate with MYCN expression in NB tumors. These results establish HSPD1 as a promising target for the treatment of MYCN-amplified NB.
ER -